Trial Outcomes & Findings for A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Negative Chronic Hepatitis B (NCT NCT00117676)

NCT ID: NCT00117676

Last Updated: 2017-03-07

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: 382 participants
• Primary outcome timeframe: Baseline; Week 48
• Results posted on: 2017-03-07

Participant Flow

Participants were enrolled at study sites in North America, Europe, and Australia/New Zealand. The first participant was screened on 07 June 2005. The last study visit occurred on 19 January 2016.

846 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; as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) to their treatment regimen 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 (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
Double-blind Period Through Week 48 STARTED	254	128
Double-blind Period Through Week 48 COMPLETED	244	121
Double-blind Period Through Week 48 NOT COMPLETED	10	7
Open-label Period: Weeks 49 - 96 STARTED	235	112
Open-label Period: Weeks 49 - 96 COMPLETED	225	110
Open-label Period: Weeks 49 - 96 NOT COMPLETED	10	2
Open-label Period: Weeks 97 - 144 STARTED	225	110
Open-label Period: Weeks 97 - 144 COMPLETED	219	109
Open-label Period: Weeks 97 - 144 NOT COMPLETED	6	1
Open-label Period: Weeks 145 - 192 STARTED	219	109
Open-label Period: Weeks 145 - 192 COMPLETED	209	106
Open-label Period: Weeks 145 - 192 NOT COMPLETED	10	3
Open-label Period: Weeks 193 - 240 STARTED	209	106
Open-label Period: Weeks 193 - 240 COMPLETED	202	103
Open-label Period: Weeks 193 - 240 NOT COMPLETED	7	3
Open-label Period: Weeks 241 - 288 STARTED	202	103
Open-label Period: Weeks 241 - 288 COMPLETED	192	100
Open-label Period: Weeks 241 - 288 NOT COMPLETED	10	3
Open-label Period: Weeks 289 - 336 STARTED	192	100
Open-label Period: Weeks 289 - 336 COMPLETED	183	93
Open-label Period: Weeks 289 - 336 NOT COMPLETED	9	7
Open-label Period: Weeks 337 - 384 STARTED	183	93
Open-label Period: Weeks 337 - 384 COMPLETED	176	90
Open-label Period: Weeks 337 - 384 NOT COMPLETED	7	3
Open-label Period: Weeks 385 - 432 STARTED	82	46
Open-label Period: Weeks 385 - 432 COMPLETED	82	44
Open-label Period: Weeks 385 - 432 NOT COMPLETED	0	2
Open-label Period: Weeks 433 - 480 STARTED	82	43
Open-label Period: Weeks 433 - 480 COMPLETED	80	41
Open-label Period: Weeks 433 - 480 NOT COMPLETED	2	2

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; as part of FTC 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet) to their treatment regimen 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 (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
Double-blind Period Through Week 48 Randomized but Not Treated	4	3
Double-blind Period Through Week 48 Lost to Follow-up	1	0
Double-blind Period Through Week 48 Protocol Violation	0	1
Double-blind Period Through Week 48 Safety, Tolerability, or Efficacy Reason	5	2
Double-blind Period Through Week 48 Withdrew Consent	0	1
Open-label Period: Weeks 49 - 96 Lost to Follow-up	2	0
Open-label Period: Weeks 49 - 96 Safety, Tolerability, or Efficacy Reason	3	1
Open-label Period: Weeks 49 - 96 Withdrew Consent	5	1
Open-label Period: Weeks 97 - 144 Lost to Follow-up	4	1
Open-label Period: Weeks 97 - 144 Safety, Tolerability, or Efficacy Reason	1	0
Open-label Period: Weeks 97 - 144 Withdrew Consent	1	0
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 Withdrew Consent	5	2
Open-label Period: Weeks 193 - 240 Investigator's Discretion	1	1
Open-label Period: Weeks 193 - 240 Lost to Follow-up	0	1
Open-label Period: Weeks 193 - 240 Safety, Tolerability, or Efficacy Reason	2	0
Open-label Period: Weeks 193 - 240 Withdrew Consent	4	1
Open-label Period: Weeks 241 - 288 Investigator's Discretion	0	1
Open-label Period: Weeks 241 - 288 Lost to Follow-up	2	1
Open-label Period: Weeks 241 - 288 Protocol Violation	2	0
Open-label Period: Weeks 241 - 288 Safety, Tolerability, or Efficacy Reason	1	0
Open-label Period: Weeks 241 - 288 Withdrew Consent	5	1
Open-label Period: Weeks 289 - 336 Investigator's Discretion	7	4
Open-label Period: Weeks 289 - 336 Lost to Follow-up	2	2
Open-label Period: Weeks 289 - 336 Withdrew Consent	0	1
Open-label Period: Weeks 337 - 384 Investigator's Discretion	1	1
Open-label Period: Weeks 337 - 384 Lost to Follow-up	3	1
Open-label Period: Weeks 337 - 384 Study Site Discontinued	1	0
Open-label Period: Weeks 337 - 384 Withdrew Consent	2	1
Open-label Period: Weeks 385 - 432 Investigator's Discretion	0	1
Open-label Period: Weeks 385 - 432 Safety, Tolerability, or Efficacy Reason	0	1
Open-label Period: Weeks 433 - 480 Lost to Follow-up	1	0
Open-label Period: Weeks 433 - 480 Safety, Tolerability, or Efficacy Reason	1	1
Open-label Period: Weeks 433 - 480 Withdrew Consent	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	TDF-TDF n=250 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=125 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=375 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	247 Participants n=5 Participants	123 Participants n=7 Participants	370 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	44 years STANDARD_DEVIATION 10.6 • n=5 Participants	43 years STANDARD_DEVIATION 10.0 • n=7 Participants	44 years STANDARD_DEVIATION 10.4 • n=5 Participants
Gender Female	57 Participants n=5 Participants	28 Participants n=7 Participants	85 Participants n=5 Participants
Gender Male	193 Participants n=5 Participants	97 Participants n=7 Participants	290 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	63 participants n=5 Participants	30 participants n=7 Participants	93 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized White	161 participants n=5 Participants	81 participants n=7 Participants	242 participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	11 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Greece	19 participants n=5 Participants	9 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Spain	15 participants n=5 Participants	6 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Turkey	11 participants n=5 Participants	3 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Italy	6 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United Kingdom	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment France	13 participants n=5 Participants	5 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Czech Republic	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Canada	29 participants n=5 Participants	18 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment Poland	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Region of Enrollment Australia	14 participants n=5 Participants	8 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Bulgaria	49 participants n=5 Participants	23 participants n=7 Participants	72 participants n=5 Participants
Region of Enrollment Germany	19 participants n=5 Participants	11 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment New Zealand	24 participants n=5 Participants	12 participants n=7 Participants	36 participants n=5 Participants
Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range Yes	236 participants n=5 Participants	118 participants n=7 Participants	354 participants n=5 Participants
Baseline Alanine Aminotransferase (ALT) Above the Upper Limit of the Normal (ULN) Range No	14 participants n=5 Participants	7 participants n=7 Participants	21 participants n=5 Participants
Prior Lamivudine or FTC Treatment Yes	43 participants n=5 Participants	23 participants n=7 Participants	66 participants n=5 Participants
Prior Lamivudine or FTC Treatment No	207 participants n=5 Participants	102 participants n=7 Participants	309 participants n=5 Participants
Baseline Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA)	6.86 log10 copies/mL STANDARD_DEVIATION 1.308 • n=5 Participants	6.98 log10 copies/mL STANDARD_DEVIATION 1.266 • n=7 Participants	6.90 log10 copies/mL STANDARD_DEVIATION 1.294 • n=5 Participants
Baseline Knodell Necroinflammatory Score	7.8 units on a scale STANDARD_DEVIATION 2.45 • n=5 Participants	7.8 units on a scale STANDARD_DEVIATION 2.20 • n=7 Participants	7.8 units on a scale STANDARD_DEVIATION 2.37 • 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=250 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-TDF n=125 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 Yes	70.8 percentage of participants	48.8 percentage of participants	—	—
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 No	29.2 percentage of participants	51.2 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=250 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-TDF n=125 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	93.2 percentage of participants	63.2 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 had discontinued unless the reason for discontinuation was unrelated to protocol criteria.

Outcome measures

Measure	TDF-TDF n=234 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-TDF n=122 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 96	90.6 percentage of participants	89.3 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=241 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-TDF n=121 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	86.7 percentage of participants	88.4 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 192	84.0 percentage of participants	86.8 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 240	82.8 percentage of participants	83.9 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 288	80.5 percentage of participants	82.9 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 336	77.0 percentage of participants	78.0 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 Week 384	74.3 percentage of participants	76.3 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=82 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-TDF n=44 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	97.6 percentage of participants	97.7 percentage of participants	—	—
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 Week 480	100.0 percentage of participants	100.0 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=241 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-TDF n=117 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 48	-4.57 log10 copies/mL Standard Deviation 1.347	-4.07 log10 copies/mL Standard Deviation 1.331	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-4.54 log10 copies/mL Standard Deviation 1.400	-4.74 log10 copies/mL Standard Deviation 1.260	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-4.61 log10 copies/mL Standard Deviation 1.285	-4.77 log10 copies/mL Standard Deviation 1.285	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-4.56 log10 copies/mL Standard Deviation 1.371	-4.75 log10 copies/mL Standard Deviation 1.271	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-4.59 log10 copies/mL Standard Deviation 1.288	-4.77 log10 copies/mL Standard Deviation 1.303	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-4.61 log10 copies/mL Standard Deviation 1.310	-4.81 log10 copies/mL Standard Deviation 1.310	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-4.61 log10 copies/mL Standard Deviation 1.329	-4.81 log10 copies/mL Standard Deviation 1.307	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-4.56 log10 copies/mL Standard Deviation 1.333	-4.79 log10 copies/mL Standard Deviation 1.314	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-4.60 log10 copies/mL Standard Deviation 1.376	-4.69 log10 copies/mL Standard Deviation 1.370	—	—
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-4.57 log10 copies/mL Standard Deviation 1.329	-4.75 log10 copies/mL Standard Deviation 1.349	—	—

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=220 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-TDF n=109 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 336	-0.05 log10 copies/mL Standard Deviation 0.380	-0.65 log10 copies/mL Standard Deviation 1.230	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-0.02 log10 copies/mL Standard Deviation 0.241	-0.66 log10 copies/mL Standard Deviation 1.237	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	0.02 log10 copies/mL Standard Deviation 0.424	-0.60 log10 copies/mL Standard Deviation 1.138	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-0.03 log10 copies/mL Standard Deviation 0.378	-0.63 log10 copies/mL Standard Deviation 1.169	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	0.01 log10 copies/mL Standard Deviation 0.610	-0.61 log10 copies/mL Standard Deviation 1.161	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-0.04 log10 copies/mL Standard Deviation 0.299	-0.61 log10 copies/mL Standard Deviation 1.195	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-0.04 log10 copies/mL Standard Deviation 0.353	-0.64 log10 copies/mL Standard Deviation 1.203	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-0.04 log10 copies/mL Standard Deviation 0.393	-0.67 log10 copies/mL Standard Deviation 1.378	—	—
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-0.05 log10 copies/mL Standard Deviation 0.366	-0.72 log10 copies/mL Standard Deviation 1.283	—	—

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=250 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-TDF n=125 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	72.4 percentage of participants	68.8 percentage of participants	—	—
Percentage of Participants With Histological Response at Week 48 No	27.6 percentage of participants	31.2 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=150 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-TDF n=74 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	87.3 percentage of participants	85.1 percentage of participants	—	—
Percentage of Participants With Histological Response at Week 240 No	12.7 percentage of participants	14.9 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=234 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-TDF n=113 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	-3.5 units on a scale Standard Deviation 2.50	-3.4 units on a scale Standard Deviation 2.36	—	—
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 Ishak Necroinflammatory Score	-2.6 units on a scale Standard Deviation 1.93	-2.6 units on a scale Standard Deviation 1.90	—	—

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=150 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-TDF n=74 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 Score	-4.6 units on a scale Standard Deviation 2.50	-4.9 units on a scale Standard Deviation 2.53	—	—
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 Ishak Score	-4.0 units on a scale Standard Deviation 2.16	-4.2 units on a scale Standard Deviation 2.38	—	—

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=250 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-TDF n=125 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	82.0 percentage of participants	81.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 No Change - Necroinflammation	6.8 percentage of participants	8.0 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Worsening - Necroinflammation	4.8 percentage of participants	0.8 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Missing Data - Necroinflammation	6.4 percentage of participants	9.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Improvement - Fibrosis	22.0 percentage of participants	25.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 No Change - Fibrosis	63.2 percentage of participants	54.4 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Worsening - Fibrosis	8.4 percentage of participants	10.4 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 48 Missing Data - Fibrosis	6.4 percentage of participants	9.6 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=150 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-TDF n=74 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 Improvement - Fibrosis	62.0 percentage of participants	59.5 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 No Change - Fibrosis	34.0 percentage of participants	33.8 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Worsening - Fibrosis	4.0 percentage of participants	6.8 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Improvement - Necroinflammation	96.7 percentage of participants	94.6 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 No Change - Necroinflammation	2.7 percentage of participants	1.4 percentage of participants	—	—
Ranked Assessment of Necroinflammation and Fibrosis at Week 240 Worsening - Necroinflammation	0.7 percentage of participants	4.1 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=236 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-TDF n=118 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 48	76.3 percentage of participants	77.1 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=221 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-TDF n=111 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 96	72.4 percentage of participants	68.5 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=226 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-TDF n=110 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	74.3 percentage of participants	70.0 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 192	68.2 percentage of participants	76.4 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 240	70.3 percentage of participants	75.7 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 288	69.9 percentage of participants	72.9 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 336	65.9 percentage of participants	65.4 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 Week 384	65.3 percentage of participants	69.2 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=74 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-TDF n=39 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	86.5 percentage of participants	87.2 percentage of participants	—	—
Percentage of Participants With ALT Normalization at Weeks 432 and 480 Week 480	80.0 percentage of participants	88.9 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=240 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-TDF n=117 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	-95.0 units per liter Standard Deviation 102.31	-124.4 units per liter Standard Deviation 137.23	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 96	-93.7 units per liter Standard Deviation 106.66	-138.5 units per liter Standard Deviation 155.75	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-99.1 units per liter Standard Deviation 105.67	-140.0 units per liter Standard Deviation 155.43	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	-99.6 units per liter Standard Deviation 109.46	-140.3 units per liter Standard Deviation 153.89	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-97.7 units per liter Standard Deviation 104.32	-139.5 units per liter Standard Deviation 156.90	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-98.9 units per liter Standard Deviation 104.66	-134.7 units per liter Standard Deviation 152.90	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-98.9 units per liter Standard Deviation 106.50	-143.1 units per liter Standard Deviation 160.15	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-96.1 units per liter Standard Deviation 105.43	-132.6 units per liter Standard Deviation 142.09	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-97.0 units per liter Standard Deviation 115.09	-131.9 units per liter Standard Deviation 136.65	—	—
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-94.9 units per liter Standard Deviation 117.60	-129.2 units per liter Standard Deviation 139.24	—	—

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=219 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-TDF n=108 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 96	2.4 units per liter Standard Deviation 22.01	-0.6 units per liter Standard Deviation 19.87	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 144	-0.6 units per liter Standard Deviation 12.91	-0.3 units per liter Standard Deviation 22.48	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 192	0.7 units per liter Standard Deviation 23.07	-3.6 units per liter Standard Deviation 22.77	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 240	-2.5 units per liter Standard Deviation 14.64	-3.9 units per liter Standard Deviation 20.00	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 288	-3.9 units per liter Standard Deviation 13.35	-4.1 units per liter Standard Deviation 22.30	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 336	-2.6 units per liter Standard Deviation 15.69	-2.0 units per liter Standard Deviation 20.61	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 384	-2.9 units per liter Standard Deviation 14.13	-3.9 units per liter Standard Deviation 21.00	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 432	-4.6 units per liter Standard Deviation 15.65	-8.9 units per liter Standard Deviation 29.12	—	—
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 Week 480	-2.8 units per liter Standard Deviation 15.92	-5.9 units per liter Standard Deviation 24.12	—	—

SECONDARY outcome

Timeframe: Baseline; Week 48

Population: Participants in the Randomized and Treated Analysis Set were analyzed. The missing = failure approach was used.

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=250 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-TDF n=125 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 Antibody to HBs (Anti-HBs) at Week 48 HBsAg Loss	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 Seroconversion to anti-HBs	0 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 96

Population: Randomized and Treated Analysis Set. 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 Week 96. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative at baseline to positive at Week 96.

Outcome measures

Measure	TDF-TDF n=242 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-TDF n=121 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 and/or Seroconversion to Anti-HBs at Week 96 HBsAg Loss	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 Anti-HBs Seroconversion	0 percentage of participants	0 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=250 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-TDF n=123 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 and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 384	0.8 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 144	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 144	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 192	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 192	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 240	0 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 240	0 percentage of participants	0 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 288	0 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 288	0 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 336	0 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 336	0 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 384	0.4 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 432	1.2 percentage of participants	1.6 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 432	0.4 percentage of participants	0.8 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 HBsAg Loss - Week 480	1.2 percentage of participants	2.4 percentage of participants	—	—
Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 Anti-HBs Seroconversion - Week 480	0.8 percentage of participants	0.8 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 at Week 48, those with viral breakthrough, and those who discontinued after Week 24 with HBV DNA ≥ 400 copies/mL.

Outcome measures

Measure	TDF-TDF n=250 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-TDF n=125 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) Changes at conserved sites in HBV polymerase	0 participants	7 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	3 participants	14 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Unable to be genotyped	1 participants	1 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) Participants evaluated	8 participants	42 participants	—	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) No genotypic changes (wild-type virus)	4 participants	20 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=235 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-TDF n=2 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=112 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 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	6 participants	1 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	0 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	2 participants	1 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) No genotypic changes (wild-type virus)	4 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) Unable to be genotyped	0 participants	0 participants	0 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=220 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-TDF n=3 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=110 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 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	4 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	0 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	1 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) No genotypic changes (wild-type virus)	2 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) Unable to genotype	1 participants	0 participants	0 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=215 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-TDF n=3 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=109 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 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	3 participants	1 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	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	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) No genotypic changes (wild-type virus)	1 participants	1 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) Unable to genotype	1 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=204 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-TDF n=3 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=105 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 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	1 participants	2 participants	2 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	1 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Changes at polymorphic sites in HBV polymerase	0 participants	2 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) No genotypic changes (wild-type virus)	0 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) Unable to genotype	0 participants	0 participants	2 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=195 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-TDF n=3 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=102 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 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) No genotypic changes (wild-type virus)	1 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Participants evaluated	3 participants	1 participants	1 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	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	2 participants	1 participants	1 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) Unable to genotype	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=189 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-TDF n=3 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=97 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 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) Changes at polymorphic sites in HBV polymerase	0 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Participants evaluated	0 participants	1 participants	1 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	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	1 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) Unable to genotype	0 participants	0 participants	1 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=177 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-TDF n=3 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=92 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 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	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	0 participants	0 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	0 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	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) Unable to genotype	1 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=81 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-TDF n=1 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=46 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 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	2 participants	0 participants	1 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	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	0 participants	0 participants	1 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) No genotypic changes (wild-type virus)	2 participants	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) Unable to genotype	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=81 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-TDF n=1 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=43 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 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	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Changes at conserved sites within HBV polymerase	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	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	0 participants	0 participants	—
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) Unable to genotype	0 participants	0 participants	0 participants	—

Adverse Events

Double-Blind TDF

Serious events: 12 serious events

Other events: 121 other events

Deaths: 0 deaths

Double-Blind ADV

Serious events: 7 serious events

Other events: 61 other events

Deaths: 0 deaths

Open-Label TDF

Serious events: 90 serious events

Other events: 256 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-Blind TDF n=250 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=125 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=347 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 384), 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 (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
Blood and lymphatic system disorders Anaemia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 unstable	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Atrial fibrillation	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Coronary artery disease	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Myocardial infarction	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Myocardial ischaemia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Sinus bradycardia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Sinus node dysfunction	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Endocrine disorders Hyperparathyroidism	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Eye disorders Lens disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 hernia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Colitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Gastrooesophageal reflux disease	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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 Haemorrhoidal haemorrhage	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Haemorrhoids	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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	0.40% 1/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Intestinal obstruction	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Pancreatitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Pancreatitis acute	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Small intestinal obstruction	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Umbilical hernia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.2% 4/347 • 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 Condition aggravated	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Granuloma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Malaise	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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 acute	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Hepatic cirrhosis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Liver disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 limb	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Appendicitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.86% 3/347 • 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 Cellulitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Erysipelas	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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 Liver abscess	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Lower respiratory tract infection	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Lung infection	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Pneumonia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.4% 5/347 • 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 Pneumonia pneumococcal	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Septic shock	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Wound infection	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Arterial injury	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Concussion	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Fall	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Foot fracture	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Hand fracture	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Head injury	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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 Injury	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Limb injury	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Meniscus injury	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Overdose	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Post procedural haemorrhage	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 hypotension	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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 Road traffic accident	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Tibia fracture	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Wound	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Wrist fracture	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	1.2% 3/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.
Investigations Hepatitis B DNA increased	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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 Diabetic ketoacidosis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Bone cyst	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Bursitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Intervertebral disc protrusion	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.86% 3/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Myopathy toxic	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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 Osteitis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Osteopenia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Spinal osteoarthritis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Tenosynovitis stenosans	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Adenocarcinoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Bladder neoplasm	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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) Cervix carcinoma	0.40% 1/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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) Cholangiocarcinoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 cancer	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 neoplasm	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Craniopharyngioma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Endometrial adenocarcinoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Gastric cancer	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Gastrointestinal carcinoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.80% 2/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	2.3% 8/347 • 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) Leiomyoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Leukaemia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Liposarcoma	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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 adenocarcinoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 neoplasm malignant	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Metastases to peritoneum	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Metastatic gastric cancer	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Mixed hepatocellular cholangiocarcinoma	0.40% 1/250 • 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% 0/125 • 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% 0/347 • 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) Nasopharyngeal cancer	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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) Non-small cell lung cancer	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Salivary gland adenoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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) Uterine leiomyoma	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Cerebral infarction	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Epilepsy	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 neuralgia	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • 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% 0/347 • 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 Loss of consciousness	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Sciatica	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Syncope	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Agitation	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Bipolar disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Delusional disorder, unspecified type	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Depression	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Dissociative disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Psychotic disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.58% 2/347 • 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 Schizophrenia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Schizophrenia, paranoid type	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Renal colic	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Renal failure	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Urogenital fistula	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Benign prostatic hyperplasia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Fibrocystic breast disease	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Bronchiectasis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Dyspnoea	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Hypoxia	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Lung disorder	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Arteritis	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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 Haematoma	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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	0.00% 0/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.29% 1/347 • 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=250 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=125 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=347 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 384), 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 (as part of FTC 200 mg/TDF 300 mg FDC tablet) to their treatment regimen in the open-label period.
Gastrointestinal disorders Abdominal pain	4.4% 11/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.8% 6/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.2% 25/347 • 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	8.8% 22/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.0% 10/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	10.4% 36/347 • 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	6.4% 16/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.4% 8/125 • 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% 31/347 • 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 Dyspepsia	2.4% 6/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.8% 6/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.6% 23/347 • 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	6.0% 15/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.8% 6/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.0% 14/347 • 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	5.2% 13/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.2% 9/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.8% 20/347 • 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	2.4% 6/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	1.6% 2/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.6% 23/347 • 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	2.0% 5/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.2% 18/347 • 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	4.0% 10/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	2.4% 3/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	11.0% 38/347 • 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	8.8% 22/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	9.6% 12/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	17.9% 62/347 • 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	2.4% 6/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.0% 5/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.9% 24/347 • 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 pain	4.4% 11/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	7.2% 9/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.2% 11/347 • 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	0.80% 2/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.0% 5/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.8% 20/347 • 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	0.00% 0/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	0.80% 1/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.6% 30/347 • 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	6.4% 16/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	11.0% 38/347 • 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	7.2% 18/250 • 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% 7/125 • 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% 54/347 • 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 Osteopenia	0.40% 1/250 • 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% 0/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.6% 30/347 • 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	4.4% 11/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.2% 4/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	5.2% 18/347 • 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	10.4% 26/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	13.6% 17/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	14.1% 49/347 • 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	4.4% 11/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	3.2% 4/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	8.6% 30/347 • 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	2.8% 7/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.8% 6/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	6.6% 23/347 • 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	3.6% 9/250 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	4.0% 5/125 • Baseline to Week 480 Randomized and Treated Analysis Set: all participants who were randomized and received at least one dose of study drug.	15.3% 53/347 • 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