TDF in CHB: Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) 300mg in Chinese Subjects With Chronic Hepatitis B (CHB)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01300234
• Collaborator: (none)
• Enrollment: 512
• Locations: 20
• Arms: 2
• Actual Duration (Months): 68.3
• Patients Per Site: 25.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a multi-centre, double blind, double dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. This study is designed to demonstrate the superiority of TDF 300mg QD over ADV 10mg QD in treating Chinese subjects with CHB (hepatitis B e antigen [HBeAg] positive subjects and HBeAg negative subjects). It will also provide long-term efficacy and safety data (up to 240 weeks) for TDF 300 mg administered once daily.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Drug: Tenofovir disoproxil fumarate (TDF) tablets; Drug: Adefovir dipivoxil (ADV) tablets	Phase 3

Detailed Description

This is a multi-centre, double-blind, double-dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. Four hundred and ninety-four subjects with CHB (200 HBeAg positive subjects and 294 HBeAg negative subjects) will be randomised (1:1ratio) to either TDF 300mg QD or ADV 10mg QD treatment arms. The primary endpoint is the proportion of subjects with blood hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <400copies/mL (Roche COBAS Taqman HBV test) at Week 48 in HBeAg positive subjects with CHB and HBeAg negative subjects with CHB. This is a two-part study. The first treatment period (baseline to Week 48) will investigate the effects of TDF and ADV on safety and efficacy endpoints; dosing will be double-blind. This period will be followed by 192 weeks in which all subjects will receive open-label TDF (Week 49 to Week 240). Subjects will undergo regular safety and efficacy assessments every 4 weeks for the first 12 weeks followed by every 12 weeks for a total of up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 512 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-centre, Double Blind, Double Dummy, Randomised, Controlled Study to Evaluate the Efficacy and Safety of TDF 300mg Once Daily (QD) Versus Adefovir Dipivoxil (ADV) 10mg QD in Chinese Subjects With CHB
• Actual Study Start Date: Mar 30, 2011
• Actual Primary Completion Date: Oct 17, 2012
• Actual Study Completion Date: Dec 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A (TDF tablets) Tenofovir disoproxil fumarate (TDF) tablets	Drug: Tenofovir disoproxil fumarate (TDF) tablets; white, almond-shaped, film-coated tablets containing 300mg of TDF; Other Names: TDF tablet
Active Comparator: B (ADV tablets) Adefovir dipivoxil (ADV) tablets	Drug: Adefovir dipivoxil (ADV) tablets; white to off-white, round, biconvex tablets containing 10mg of ADV; Other Names: ADV tablet

Outcome Measures

Primary Outcome Measures

1. Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48 [Week 48]

   The number of participants with Hepatitis B Virus (HBV) deoxyribonucleic acid (DNA) <400 copies/milliliter (mL) at Week 48 in the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually, a negative result indicates that the participant has lower levels of virus in the blood and is less infectious. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

Secondary Outcome Measures

1. Participants With HBV DNA <400 Copies/mL at Weeks 96, 144, 192, and 240 [Weeks 96, 144, 192, and 240]

   The number of participants with HBV DNA <400 copies/mL in the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually, a negative result indicates that the participant has lower levels of virus in the blood and is less infectious. Week 96, 144, 192, and 240 data are not yet available, as this report includes data up to and including Week 48. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

2. Change From Baseline of Log 10 Copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240 [Baseline, Weeks 48, 96, 144, 192 and 240]

   Change from Baseline of log 10 copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240 in the HBeAg-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually a negative result indicates that the participant has lower levels of virus in the blood and less infectious. Values at Day 0 were considered as Baseline values. Change from Baseline was calculated as post Baseline values minus Baseline values. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

3. Number of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, 144, 192 and 240 in Participants Who Had Abnormal ALT at Baseline [Baseline; Weeks 48, 96, 144, 192 and 240]

   Participants who had abnormal ALT at Baseline and had normalized ALT at Weeks 48, 96, 144, 192 and 240 were assessed. This report includes data up to and including Weeks 48, 96, 144, 192 and 240. An increased level of ALT is referred to as abnormal ALT (the normal range is 0 to 48 units per liter [U/L]). Values at Day 0 were considered as Baseline values. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

4. Number of Participants With Histological Improvement at Weeks 48 and 240 Who Had a Baseline Knodell Necroinflammatory Score (KNS) >=2. [Baseline; Week 48 and Week 240]

   Histological improvement is defined as a reduction of >=2 points in the KNS with no increase in fibrosis at Week 48 and Week 240 in participants with Baseline KNS >=2 which was derived from the American Association for the Study of Liver Diseases Practice Guidelines for Management of Chronic Hepatitis B (2009) and the European Association for the Study of the Liver Clinical Practice Guidelines Management of chronic hepatitis B virus infection (2012). The Knodell scale consists of 5 domains: periportal +/- bridging necrosis (scored from best to worst: 0, 1, 3, 4, 5, 6, or 10); intralobular degeneration and focal necrosis (0 to 4); portal inflammation (0 to 4); and fibrosis (0 to 4). The necroinflammatory score (ranging from 0 [best] to 14 [worst]) is the combined score for necrosis (0 to 10) plus inflammation (0 to 4; the participant is scored for only one inflammatory condition). Liver biopsy slides within 6 months prior to randomization could be accepted as Baseline evaluation.

5. Number of HBeAg-positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240. [Weeks 24, 48, 96, 144, 192 and 240]

   HBeAg loss is defined as a negative HBeAg result for those participants who were HBeAg positive at Baseline. Seroconversion to anti-HBe is defined as HBeAg loss and a positive anti-HBe result. This report includes data up to and including Weeks 24, 48, 96, 144, 192 and 240.

6. Number of HBeAg-positive Participants Achieving Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240 [Weeks 24, 48, 96, 144, 192 and 240]

   HBsAg loss is defined as negative HBsAg results for those participants with who were HBsAg positive at Baseline. Seroconversion to anti-HBs is defined as HBsAg loss and a positive anti-HBs result. This report includes data up to and including Week 240.

7. Number of HBeAg-negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192, 240 [Weeks 24, 48, 96, 144, 192 and 240]

   HBsAg loss is defined as a negative HBsAg result for those participants with who were HBsAg positive at Baseline. Seroconversion to anti-HBs is defined as HBsAg loss and a positive anti-HBs result. This report includes data up to and including Week 240.

8. Number of Participants Achieving Durable HBsAg Loss From Weeks 24 to Week 48 [Week 24 to Week 48]

   Durable HBsAg loss is defined as the loss of HBsAg and no detectable HBV DNA and ALT normalization at any three consecutive visits at least 12 Weeks apart. This report includes data up to and including Week 48. A "non-completers equal failures" approach was used for the analysis in ITT population.

9. Number of Participants Achieving Durable HBsAg Loss From Weeks 96 to Week 240 [Week 96 to Week 240]

   Durable HBsAg loss is defined as the loss of HBsAg and no detectable HBV DNA and ALT normalization at any three consecutive visits at least 12 Weeks apart from Week 96 to 240. This report includes data up to and including Week 240. A "non-completers equal failures" approach was used for the analysis in ITT population.

10. Number of Participants With Virological Breakthrough at Weeks 48, 96, 144, 192 and 240 [Weeks 48, 96, 144, 192 and 240]

    The number of HBeAg-positive and HBeAg-negative participants who had virological breakthrough at Weeks 48, 96, 144, 192 and 240 were assessed. Virological breakthrough is defined by >= one log increase in HBV DNA from NADIR (as determined by two sequential HBV DNA measurements at least one month apart or last on treatment measurement). A "non-completers equal failures" approach was used for the analysis in ITT population.

11. Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE) [Up to Week 240 treatment period and 24 weeks follow-up visit off treatment]

    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is Grade 4 (life threatening or disabling). Participants with any non-serious AEs and SAEs has been reported.

12. Number of Participants With the Indicated Grade 3 and Grade 4 Treatment-emergent (TE) Laboratory Abnormalities (LAs) [Up to Week 240]

    TE grade 3 or grade 4 LAs are defined as values that increase by >=1 grade from Baseline (Day 0) to Grade 3 (severe) or 4 (potentially life threatening) at any post-Baseline value. The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was referred for grading. Laboratory parameters assessed included Sodium for hyponatremia and hypernatremia; Potassium for hypokalemia and hyperkalemia; glucose for hypoglycemia and hyperglycemia non-fasting; Phosphate for hypophosphatemia; alanine aminotransferase/aspartate aminotransferase, bilirubin, creatinine kinase, hemoglobin, platelets, neutrophils, lymphocytes, prothrombin time and amylase.

13. Number of Participants With the Indicated Treatment-emergent Laboratory Abnormalities for Serum Creatinine and Serum Phosphorus [Up to Week 240]

    The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was referred for grading. Serum creatinine: Grade 1, > 133 to 177 micromoles per Liter (µmoles/Liter), Grade 2, >177 to 265 µmoles/Liter, Grade 3, >265 to 530 µmoles/Liter, Grade 4, >530 µmoles/Liter. Serum phosphorus: Grade 2, 0.63 to <0.80 millimoles per Liter (mmoles/L), Grade 3, 0.31 to <0.63 mmoles/L, Grade 4, <0.31 mmoles/L. The normal range for serum phosphorus was 0.8 to 1.45 mmoles/L; the upper limit for a Grade 2 abnormality is 0.80 mmoles/L. Therefore, no Grade 1 abnormalities could be attributed, as values were contained within the normal range. NA indicates the value was not available for the indicated time point.

14. Number of Participants in the Indicated Category for Renal Laboratory Abnormalities [Up to Week 240]

    The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was used for grading. "Confirmed" is defined as two consecutive visits. mg=milligrams. dL=deciliter, G= Grade.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HBeAg positive/negative CHB with blood HBVDNA≥10^5 copies/mL and elevated ALT

• Nucleoside and nucleotide naïve CHB subjects. Previous lamivudine treatment is allowed in less than 10% of the total study population

Exclusion Criteria:

• subjects with hepatocellular carcinoma (HCC) potential or decompensated liver disease

• subjects with acute liver disease due to other causes

• subjects with medication history of immunosuppressive therapy, immunomodulatory therapy, systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine, hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to randomisation into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Guangzhou	Guangdong	China	510060
2	GSK Investigational Site	Guangzhou	Guangdong	China	510515
3	GSK Investigational Site	Guangzhou	Guangdong	China	510630
4	GSK Investigational Site	Wuhan	Hubei	China	430030
5	GSK Investigational Site	Changsha	Hunan	China	410008
6	GSK Investigational Site	Nanjing	Jiangsu	China	210003
7	GSK Investigational Site	Nanjing	Jiangsu	China	210029
8	GSK Investigational Site	Changchun	Jilin	China	130021
9	GSK Investigational Site	Chengdu	Sichuan	China	610041
10	GSK Investigational Site	Hangzhou	Zhejiang	China	310003
11	GSK Investigational Site	Beijing		China	100015
12	GSK Investigational Site	Beijing		China	100044
13	GSK Investigational Site	Beijing		China	100050
14	GSK Investigational Site	Chongqing		China	400038
15	GSK Investigational Site	Fuzhou		China	350025
16	GSK Investigational Site	Jinan		China	250021
17	GSK Investigational Site	Shanghai		China	200001
18	GSK Investigational Site	Shanghai		China	200025
19	GSK Investigational Site	Shanghai		China	200040
20	GSK Investigational Site	Shanghai		China	201508

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01300234
• Other Study ID Numbers: 114648
• First Posted: Feb 21, 2011
• Last Update Posted: Jul 13, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by GlaxoSmithKline: tenofovir disoproxil fumarate; chronic hepatitis B; adefovir dipivoxil
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis; Tenofovir; Adefovir; Adefovir dipivoxil

Study Results

Participant Flow

Recruitment Details	This was a 2 sequential treatment period study. In first period (double-blinded),participants received tenofovir disoproxil fumarate (TDF) 300 milligram (mg) once daily (QD) or adefovir dipivoxil (ADV) 10 mg QD for 48 Weeks. In second period (open-label single treatment), participants received TDF 300 mg QD for additional 192 Weeks.
Pre-assignment Detail	969 participants were screened, 512 were randomized and 509 were treated with at least one dose of study medication in the double-blind treatment period. Participants who received at least one dose of study medication continued in open-label period.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Period Title: Overall Study
STARTED	257	255
COMPLETED	229	228
NOT COMPLETED	28	27

Baseline Characteristics

Arm/Group Title	TDF-TDF	ADV-TDF	Total
Arm/Group Description	In first treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second treatment, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second treatment, participants self-administered TDF 300 mg QD for additional 192 Weeks.	Total of all reporting groups
Overall Participants	257	252	509
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.1 (10.48)	36.4 (10.43)	36.3 (10.44)
Sex: Female, Male (Count of Participants)
Female	43 16.7%	42 16.7%	85 16.7%
Male	214 83.3%	210 83.3%	424 83.3%
Race/Ethnicity, Customized (participants) [Number]
Asian - East Asian Heritage	257 100%	252 100%	509 100%

Outcome Measures

1. Primary Outcome

Title	Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48
Description	The number of participants with Hepatitis B Virus (HBV) deoxyribonucleic acid (DNA) <400 copies/milliliter (mL) at Week 48 in the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually, a negative result indicates that the participant has lower levels of virus in the blood and is less infectious. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All randomized participants who received at least one dose of study medication.

Arm/Group Title	TDF 300 mg	ADV 10 mg
Arm/Group Description	Participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks.	Participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks.
Measure Participants	257	252
HBeAg-positive, n=103, 99	79 30.7%	18 7.1%
HBeAg-negative, n=154, 153	149 58%	109 43.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TDF 300 mg, ADV 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	HBeAg-positive participants
	Method	Roche COBAS Taqman HBV test
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	58.5
	Confidence Interval	(2-Sided) 97.5%; 45.8 to 71.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	A "non-completers equal failures" approach is used for the primary analysis. The estimated value represents the difference between the percentage of participants achieving HBV DNA <400 copies/mL at Week 48 in the TDF group and the ADV group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TDF 300 mg, ADV 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	HBeAg-negative participants
	Method	Roche COBAS Taqman HBV test
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	25.6
	Confidence Interval	(2-Sided) 97.5%; 16.7 to 34.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	A "non-completers equal failures" approach was used for the primary analysis. The estimated value represents the difference between the percentage of participants achieving HBV DNA <400 copies/mL at Week 48 in the TDF group and the ADV group.

2. Secondary Outcome

Title	Participants With HBV DNA <400 Copies/mL at Weeks 96, 144, 192, and 240
Description	The number of participants with HBV DNA <400 copies/mL in the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually, a negative result indicates that the participant has lower levels of virus in the blood and is less infectious. Week 96, 144, 192, and 240 data are not yet available, as this report includes data up to and including Week 48. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Time Frame	Weeks 96, 144, 192, and 240

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Week 96, HBeAg-positive, n=103, 99	95 37%	92 36.5%
Week 96, HBeAg-negative, n=154, 153	144 56%	143 56.7%
Week 144, HBeAg-positive, n=103, 99	97 37.7%	95 37.7%
Week 144, HBeAg-negative, n=154,153	144 56%	145 57.5%
Week 192, HBeAg-positive, n=103,99	94 36.6%	93 36.9%
Week 192,HBeAg-negative, n=154,153	144 56%	141 56%
Week 240, HBeAg-positive, n=103,99	87 33.9%	87 34.5%
Week 240, HBeAg-negative, n=154,153	138 53.7%	137 54.4%

3. Secondary Outcome

Title	Change From Baseline of Log 10 Copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240
Description	Change from Baseline of log 10 copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240 in the HBeAg-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually a negative result indicates that the participant has lower levels of virus in the blood and less infectious. Values at Day 0 were considered as Baseline values. Change from Baseline was calculated as post Baseline values minus Baseline values. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Time Frame	Baseline, Weeks 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Week 48,HBeAg-positive, n=102, 97	-6.4 (0.86)	-4.4 (1.69)
Week 48,HBeAg-negative, n=151, 148	-4.9 (1.16)	-4.3 (1.31)
Week 96, HBeAg-positive, n=101, 97	-6.5 (0.86)	-6.5 (0.81)
Week 96, HBeAg-negative, n=147,148	-4.9 (1.26)	-4.8 (1.17)
Week 144, HBeAg-postive, n=100, 96	-6.6 (0.86)	-6.5 (0.80)
Week 144, HBeAg-negative, n=145, 146	-4.9 (1.16)	-4.9 (1.09)
Week 192, HBeAg-positive, n=97,93	-6.6 (0.86)	-6.6 (0.81)
Week 192, HBeAg-negative, n=145,145	-4.9 (1.17)	-4.8 (1.14)
Week 240, HBeAg-positive, n=91,90	-6.6 (1.01)	-6.5 (0.79)
Week 240, HBeAg-negative, n=138,138	-4.9 (1.16)	-4.9 (1.07)

4. Secondary Outcome

Title	Number of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, 144, 192 and 240 in Participants Who Had Abnormal ALT at Baseline
Description	Participants who had abnormal ALT at Baseline and had normalized ALT at Weeks 48, 96, 144, 192 and 240 were assessed. This report includes data up to and including Weeks 48, 96, 144, 192 and 240. An increased level of ALT is referred to as abnormal ALT (the normal range is 0 to 48 units per liter [U/L]). Values at Day 0 were considered as Baseline values. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Time Frame	Baseline; Weeks 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg once daily for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg once daily for additional 192 Weeks.
Measure Participants	257	252
Week 48, HBeAg-positive, n=102, 97	88 34.2%	83 32.9%
Week 48, HBeAg-negative, n=136, 132	120 46.7%	116 46%
Week 96, HBeAg-positive, n=102, 97	93 36.2%	88 34.9%
Week 96, HBeAg-negative, n=136,132	126 49%	118 46.8%
Week 144, HBeAg-positive, n=102, 97	92 35.8%	87 34.5%
Week 144, HBeAg-negative, n=136, 132	123 47.9%	119 47.2%
Week 192, HBeAg-positive, n=102, 97	89 34.6%	79 31.3%
Week 192, HBeAg-negative, n=136,132	125 48.6%	118 46.8%
Week 240, HBeAg-positive, n=102, 97	82 31.9%	80 31.7%
Week 240, HBeAg-negative, n=136,132	119 46.3%	111 44%

5. Secondary Outcome

Title	Number of Participants With Histological Improvement at Weeks 48 and 240 Who Had a Baseline Knodell Necroinflammatory Score (KNS) >=2.
Description	Histological improvement is defined as a reduction of >=2 points in the KNS with no increase in fibrosis at Week 48 and Week 240 in participants with Baseline KNS >=2 which was derived from the American Association for the Study of Liver Diseases Practice Guidelines for Management of Chronic Hepatitis B (2009) and the European Association for the Study of the Liver Clinical Practice Guidelines Management of chronic hepatitis B virus infection (2012). The Knodell scale consists of 5 domains: periportal +/- bridging necrosis (scored from best to worst: 0, 1, 3, 4, 5, 6, or 10); intralobular degeneration and focal necrosis (0 to 4); portal inflammation (0 to 4); and fibrosis (0 to 4). The necroinflammatory score (ranging from 0 [best] to 14 [worst]) is the combined score for necrosis (0 to 10) plus inflammation (0 to 4; the participant is scored for only one inflammatory condition). Liver biopsy slides within 6 months prior to randomization could be accepted as Baseline evaluation.
Time Frame	Baseline; Week 48 and Week 240

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first treatment double-blinded period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first treatment double-blinded period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	86	102
Week 48, HBeAg-positive, n=38, 49	31 12.1%	39 15.5%
Week 48, HBeAg-negative, n=45, 50	32 12.5%	34 13.5%
Week 240, HBeAg-positive, n=38, 49	5 1.9%	2 0.8%
Week 240, HBeAg-negative, n=45, 50	8 3.1%	4 1.6%

6. Secondary Outcome

Title	Number of HBeAg-positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240.
Description	HBeAg loss is defined as a negative HBeAg result for those participants who were HBeAg positive at Baseline. Seroconversion to anti-HBe is defined as HBeAg loss and a positive anti-HBe result. This report includes data up to and including Weeks 24, 48, 96, 144, 192 and 240.
Time Frame	Weeks 24, 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at specific time point were analyzed

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	103	99
Week 24, HBeAg loss	15 5.8%	4 1.6%
Week 24, HBeAg seroconversion	14 5.4%	4 1.6%
Week 48, HBeAg loss	18 7%	10 4%
Week 48, HBeAg seroconversion	16 6.2%	9 3.6%
Week 96, HBeAg loss	37 14.4%	21 8.3%
Week 96, HBeAg seroconversion	32 12.5%	18 7.1%
Week 144, HBeAg loss	37 14.4%	24 9.5%
Week 144, HBeAg seroconversion	33 12.8%	20 7.9%
Week 192, HBeAg loss	43 16.7%	31 12.3%
Week 192, HBeAg seroconversion	33 12.8%	24 9.5%
Week 240, HBeAg loss	43 16.7%	36 14.3%
Week 240, HBeAg seroconversion	33 12.8%	28 11.1%

7. Secondary Outcome

Title	Number of HBeAg-positive Participants Achieving Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240
Description	HBsAg loss is defined as negative HBsAg results for those participants with who were HBsAg positive at Baseline. Seroconversion to anti-HBs is defined as HBsAg loss and a positive anti-HBs result. This report includes data up to and including Week 240.
Time Frame	Weeks 24, 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first treatment double-blinded period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first treatment double-blinded period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	103	99
Week 24, HBsAg loss	0 0%	0 0%
Week 24, HBsAg seroconversion	0 0%	0 0%
Week 48, HBsAg loss	0 0%	0 0%
Week 48, HBsAg seroconversion	0 0%	0 0%
Week 96, HBsAg loss	0 0%	0 0%
Week 96, HBsAg seroconversion	0 0%	0 0%
Week 144, HBsAg loss	1 0.4%	0 0%
Week 144, HBaAg seroconversion	0 0%	0 0%
Week 192, HBsAg, loss	1 0.4%	0 0%
Week 192, HBsAg, seroconversion	0 0%	0 0%
Week 240, HBsAg loss	1 0.4%	0 0%
Week 240 HBsAg seroconversion	0 0%	0 0%

8. Secondary Outcome

Title	Number of HBeAg-negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192, 240
Description	HBsAg loss is defined as a negative HBsAg result for those participants with who were HBsAg positive at Baseline. Seroconversion to anti-HBs is defined as HBsAg loss and a positive anti-HBs result. This report includes data up to and including Week 240.
Time Frame	Weeks 24, 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	154	153
Week 24, HBsAg loss	0 0%	0 0%
Week 24, HBsAg seroconversion	0 0%	0 0%
Week 48, HBsAg loss	0 0%	0 0%
Week 48, HBsAg seroconversion	0 0%	0 0%
Week 96, HBsAg loss	0 0%	0 0%
Week 96, HBsAg seroconversion	0 0%	0 0%
Week 144, HBsAg loss	0 0%	1 0.4%
Week 144, HBsAg seroconversion	0 0%	1 0.4%
Week 192, HBsAg loss	0 0%	0 0%
Week 192, HBsAg seroconversion	0 0%	0 0%
Week 240, HBsAg loss	0 0%	0 0%
Week 240, HBsAg seroconversion	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants Achieving Durable HBsAg Loss From Weeks 24 to Week 48
Description	Durable HBsAg loss is defined as the loss of HBsAg and no detectable HBV DNA and ALT normalization at any three consecutive visits at least 12 Weeks apart. This report includes data up to and including Week 48. A "non-completers equal failures" approach was used for the analysis in ITT population.
Time Frame	Week 24 to Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time points were assessed.

Arm/Group Title	TDF 300 mg	ADV 10 mg
Arm/Group Description	Participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks.	Participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks.
Measure Participants	257	252
HBeAg-positive, n =100, 97	0 0%	0 0%
HBeAg-negative, n=150, 147	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants Achieving Durable HBsAg Loss From Weeks 96 to Week 240
Description	Durable HBsAg loss is defined as the loss of HBsAg and no detectable HBV DNA and ALT normalization at any three consecutive visits at least 12 Weeks apart from Week 96 to 240. This report includes data up to and including Week 240. A "non-completers equal failures" approach was used for the analysis in ITT population.
Time Frame	Week 96 to Week 240

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
HBeAg-positive, n= 88, 90	1 0.4%	0 0%
HBeAg-negative, n = 132, 137	0 0%	1 0.4%

11. Secondary Outcome

Title	Number of Participants With Virological Breakthrough at Weeks 48, 96, 144, 192 and 240
Description	The number of HBeAg-positive and HBeAg-negative participants who had virological breakthrough at Weeks 48, 96, 144, 192 and 240 were assessed. Virological breakthrough is defined by >= one log increase in HBV DNA from NADIR (as determined by two sequential HBV DNA measurements at least one month apart or last on treatment measurement). A "non-completers equal failures" approach was used for the analysis in ITT population.
Time Frame	Weeks 48, 96, 144, 192 and 240

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Week 48,HBeAg-Positive, n=103, 99	0 0%	4 1.6%
Week 48, HBeAg-Negative, n=154, 153	0 0%	2 0.8%
Week 96, HBeAg-positive, n=103, 99	0 0%	4 1.6%
Week 96, HBeAg-negative, n=154, 153	2 0.8%	3 1.2%
Week 144, HBeAg-positive, n=103, 99	0 0%	7 2.8%
Week 144, HBeAg-negative, n=154, 153	3 1.2%	4 1.6%
Week 192, HBeAg-positive, n=103, 99	0 0%	7 2.8%
Week 192, HBeAg-negative, n=154, 153	3 1.2%	5 2%
Week 240, HBeAg-positive, n=103, 99	4 1.6%	11 4.4%
Week 240, HBeAg-negative, n=154, 153	3 1.2%	8 3.2%

12. Secondary Outcome

Title	Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE)
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is Grade 4 (life threatening or disabling). Participants with any non-serious AEs and SAEs has been reported.
Time Frame	Up to Week 240 treatment period and 24 weeks follow-up visit off treatment

Outcome Measure Data

Analysis Population Description

Safety Analysis Population: All participants who received at least one dose of study medication and had at least one post-Baseline safety assessment

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Non-serious AE	140 54.5%	121 48%
SAE	12 4.7%	20 7.9%

13. Secondary Outcome

Title	Number of Participants With the Indicated Grade 3 and Grade 4 Treatment-emergent (TE) Laboratory Abnormalities (LAs)
Description	TE grade 3 or grade 4 LAs are defined as values that increase by >=1 grade from Baseline (Day 0) to Grade 3 (severe) or 4 (potentially life threatening) at any post-Baseline value. The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was referred for grading. Laboratory parameters assessed included Sodium for hyponatremia and hypernatremia; Potassium for hypokalemia and hyperkalemia; glucose for hypoglycemia and hyperglycemia non-fasting; Phosphate for hypophosphatemia; alanine aminotransferase/aspartate aminotransferase, bilirubin, creatinine kinase, hemoglobin, platelets, neutrophils, lymphocytes, prothrombin time and amylase.
Time Frame	Up to Week 240

Outcome Measure Data

Analysis Population Description

Safety Analysis Population

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks.In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks.In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Sodium	2 0.8%	0 0%
Phosphate	2 0.8%	3 1.2%
Alanine aminotransferase	19 7.4%	14 5.6%
Aspartate aminotransferase	10 3.9%	6 2.4%
Bilirubin	1 0.4%	1 0.4%
Creatine kinase	6 2.3%	4 1.6%
Hemoglobin	4 1.6%	5 2%
Platelets	4 1.6%	3 1.2%
Neutrophils	6 2.3%	4 1.6%
Prothrombin time	10 3.9%	17 6.7%
Potassium	1 0.4%	0 0%
Glucose	1 0.4%	2 0.8%
Lymphocytes	2 0.8%	3 1.2%
Amylase	1 0.4%	2 0.8%

14. Secondary Outcome

Title	Number of Participants With the Indicated Treatment-emergent Laboratory Abnormalities for Serum Creatinine and Serum Phosphorus
Description	The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was referred for grading. Serum creatinine: Grade 1, > 133 to 177 micromoles per Liter (µmoles/Liter), Grade 2, >177 to 265 µmoles/Liter, Grade 3, >265 to 530 µmoles/Liter, Grade 4, >530 µmoles/Liter. Serum phosphorus: Grade 2, 0.63 to <0.80 millimoles per Liter (mmoles/L), Grade 3, 0.31 to <0.63 mmoles/L, Grade 4, <0.31 mmoles/L. The normal range for serum phosphorus was 0.8 to 1.45 mmoles/L; the upper limit for a Grade 2 abnormality is 0.80 mmoles/L. Therefore, no Grade 1 abnormalities could be attributed, as values were contained within the normal range. NA indicates the value was not available for the indicated time point.
Time Frame	Up to Week 240

Outcome Measure Data

Analysis Population Description

Safety Analysis Population

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Serum creatinine, Grade 1	0 0%	1 0.4%
Serum creatinine, Grade 2	0 0%	0 0%
Serum creatinine, Grade 3	0 0%	0 0%
Serum creatinine, Grade 4	0 0%	0 0%
Serum phosphorus, Grade 1	NA NaN	NA NaN
Serum phosphorus, Grade 2	42 16.3%	55 21.8%
Serum phosphorus, Grade 3	2 0.8%	3 1.2%
Serum phosphorus, Grade 4	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants in the Indicated Category for Renal Laboratory Abnormalities
Description	The Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, version 21, September 2011 was used for grading. "Confirmed" is defined as two consecutive visits. mg=milligrams. dL=deciliter, G= Grade.
Time Frame	Up to Week 240

Outcome Measure Data

Analysis Population Description

Safety Analysis Population

Arm/Group Title	TDF-TDF	ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.	In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
Measure Participants	257	252
Creatinine increase of 0.5 mg/dL above Baseline	1 0.4%	0 0%
Confirmed creatinine >=2.0 mg/dL	0 0%	0 0%
Confirmed clearance <50 milliliters/minute	0 0%	0 0%
Confirmed phosphorus G 3/4 abnormality, <2.0 mg/dL	3 1.2%	0 0%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment up to 240 weeks treatment period and 24 weeks follow-up visit off treatment.
Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in members of the Safety Analysis (SA) Population, comprised of all participants who received at least one dose of study medication and had at least one post-Baseline safety assessment.
Arm/Group Title	TDF-TDF		ADV-TDF
Arm/Group Description	In first double-blinded treatment period, participants self-administered TDF 300 mg tablets plus matching ADV placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.		In first double-blinded treatment period, participants self-administered ADV 10 mg tablets plus matching TDF placebo at the same time QD for 48 Weeks. In second open-label treatment period, participants self-administered TDF 300 mg QD for additional 192 Weeks.
All Cause Mortality
	TDF-TDF		ADV-TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/257 (0.4%)		0/252 (0%)
Serious Adverse Events
	TDF-TDF		ADV-TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/257 (4.7%)		20/252 (7.9%)
Blood and lymphatic system disorders
Lymphoid tissue hyperplasia	0/257 (0%)		1/252 (0.4%)
Cardiac disorders
Angina pectoris	0/257 (0%)		1/252 (0.4%)
Endocrine disorders
Goitre	1/257 (0.4%)		0/252 (0%)
Hyperthyroidism	1/257 (0.4%)		0/252 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/257 (0%)		1/252 (0.4%)
Chronic gastritis	0/257 (0%)		1/252 (0.4%)
Gastritis erosive	0/257 (0%)		1/252 (0.4%)
Gastrointestinal haemorrhage	1/257 (0.4%)		0/252 (0%)
Large intestine polyp	0/257 (0%)		1/252 (0.4%)
Hepatobiliary disorders
Hepatitis	0/257 (0%)		1/252 (0.4%)
Gallbladder polyp	0/257 (0%)		1/252 (0.4%)
Infections and infestations
Appendicitis	1/257 (0.4%)		0/252 (0%)
Pyelonephritis acute	0/257 (0%)		1/252 (0.4%)
Injury, poisoning and procedural complications
Ankle fracture	0/257 (0%)		1/252 (0.4%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/257 (0%)		1/252 (0.4%)
Musculoskeletal and connective tissue disorders
Synovitis	1/257 (0.4%)		0/252 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant glioma	1/257 (0.4%)		0/252 (0%)
Cholangiocarcinoma	0/257 (0%)		2/252 (0.8%)
Colon cancer	1/257 (0.4%)		0/252 (0%)
Hepatic cancer	1/257 (0.4%)		3/252 (1.2%)
Hepatic cancer recurrent	0/257 (0%)		1/252 (0.4%)
Hepatocellular carcinoma	2/257 (0.8%)		0/252 (0%)
Thyroid adenoma	1/257 (0.4%)		0/252 (0%)
Thyroid cancer	0/257 (0%)		1/252 (0.4%)
Nervous system disorders
Cubital tunnel syndrome	0/257 (0%)		1/252 (0.4%)
Cerebral infarction	0/257 (0%)		1/252 (0.4%)
Lacunar infarction	0/257 (0%)		1/252 (0.4%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/257 (0.4%)		0/252 (0%)
Foetal growth restriction	1/257 (0.4%)		0/252 (0%)
Renal and urinary disorders
Ureterolithiasis	0/257 (0%)		2/252 (0.8%)
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	1/257 (0.4%)		0/252 (0%)
Skin and subcutaneous tissue disorders
Dermal cyst	1/257 (0.4%)		0/252 (0%)
Social circumstances
Miscarriage of partner	0/257 (0%)		1/252 (0.4%)
Other (Not Including Serious) Adverse Events
	TDF-TDF		ADV-TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/257 (54.5%)		121/252 (48%)
Blood and lymphatic system disorders
Anaemia	3/257 (1.2%)		2/252 (0.8%)
Polycythaemia	0/257 (0%)		1/252 (0.4%)
Cardiac disorders
Angina pectoris	0/257 (0%)		1/252 (0.4%)
Palpitations	2/257 (0.8%)		0/252 (0%)
Prinzmetal angina	1/257 (0.4%)		0/252 (0%)
Congenital, familial and genetic disorders
Accessory spleen	0/257 (0%)		1/252 (0.4%)
Hamartoma	0/257 (0%)		1/252 (0.4%)
Ear and labyrinth disorders
Middle ear effusion	0/257 (0%)		1/252 (0.4%)
Sudden hearing loss	0/257 (0%)		1/252 (0.4%)
Tinnitus	1/257 (0.4%)		2/252 (0.8%)
Vertigo	1/257 (0.4%)		0/252 (0%)
Endocrine disorders
Hyperthyroidism	1/257 (0.4%)		1/252 (0.4%)
Hypogonadism	0/257 (0%)		1/252 (0.4%)
Thyroid mass	1/257 (0.4%)		0/252 (0%)
Eye disorders
Eye swelling	1/257 (0.4%)		0/252 (0%)
Gastrointestinal disorders
Abdominal discomfort	3/257 (1.2%)		2/252 (0.8%)
Abdominal pain upper	3/257 (1.2%)		5/252 (2%)
Abdominal distension	0/257 (0%)		1/252 (0.4%)
Abdominal pain	1/257 (0.4%)		1/252 (0.4%)
Aphthous ulcer	0/257 (0%)		1/252 (0.4%)
Ascites	2/257 (0.8%)		0/252 (0%)
Cheilitis	0/257 (0%)		1/252 (0.4%)
Diarrhoea	4/257 (1.6%)		2/252 (0.8%)
Dry mouth	1/257 (0.4%)		1/252 (0.4%)
Duodenal ulcer	1/257 (0.4%)		0/252 (0%)
Dyspepsia	0/257 (0%)		2/252 (0.8%)
Gastritis	1/257 (0.4%)		2/252 (0.8%)
Gingival swelling	1/257 (0.4%)		0/252 (0%)
Haematochezia	0/257 (0%)		1/252 (0.4%)
Mouth ulceration	2/257 (0.8%)		2/252 (0.8%)
Nausea	1/257 (0.4%)		2/252 (0.8%)
Tooth disorder	0/257 (0%)		1/252 (0.4%)
Toothache	2/257 (0.8%)		1/252 (0.4%)
General disorders
Asthenia	4/257 (1.6%)		5/252 (2%)
Chest discomfort	0/257 (0%)		2/252 (0.8%)
Chest pain	1/257 (0.4%)		3/252 (1.2%)
Chills	0/257 (0%)		1/252 (0.4%)
Fatigue	1/257 (0.4%)		2/252 (0.8%)
Pyrexia	3/257 (1.2%)		1/252 (0.4%)
Sensation of foreign body	0/257 (0%)		1/252 (0.4%)
Hepatobiliary disorders
Cholelithiasis	5/257 (1.9%)		4/252 (1.6%)
Gallbladder polyp	6/257 (2.3%)		4/252 (1.6%)
Hepatic pain	5/257 (1.9%)		5/252 (2%)
Hepatic steatosis	11/257 (4.3%)		11/252 (4.4%)
Bile duct stone	3/257 (1.2%)		2/252 (0.8%)
Cholecystitis	2/257 (0.8%)		2/252 (0.8%)
Cholecystitis acute	0/257 (0%)		1/252 (0.4%)
Hepatic cyst	0/257 (0%)		2/252 (0.8%)
Hepatic function abnormal	4/257 (1.6%)		2/252 (0.8%)
Hepatitis	2/257 (0.8%)		1/252 (0.4%)
Liver disorder	1/257 (0.4%)		0/252 (0%)
Non-alcoholic fatty liver	0/257 (0%)		1/252 (0.4%)
Non-alcoholic steatohepatitis	0/257 (0%)		1/252 (0.4%)
Perihepatic discomfort	1/257 (0.4%)		4/252 (1.6%)
Immune system disorders
Food allergy	1/257 (0.4%)		0/252 (0%)
Infections and infestations
Bronchitis	1/257 (0.4%)		4/252 (1.6%)
Gingivitis	3/257 (1.2%)		2/252 (0.8%)
Nasopharyngitis	8/257 (3.1%)		8/252 (3.2%)
Upper respiratory tract infection	34/257 (13.2%)		25/252 (9.9%)
Eczema infected	0/257 (0%)		1/252 (0.4%)
Gastroenteritis	1/257 (0.4%)		0/252 (0%)
Hepatitis B	3/257 (1.2%)		4/252 (1.6%)
Herpes simplex	0/257 (0%)		1/252 (0.4%)
Herpes zoster	1/257 (0.4%)		0/252 (0%)
Influenza	1/257 (0.4%)		0/252 (0%)
Otitis media acute	0/257 (0%)		1/252 (0.4%)
Pharyngitis	2/257 (0.8%)		2/252 (0.8%)
Tonsillitis	2/257 (0.8%)		0/252 (0%)
Tonsillitis bacterial	0/257 (0%)		1/252 (0.4%)
Viral rash	1/257 (0.4%)		0/252 (0%)
Injury, poisoning and procedural complications
Animal bite	0/257 (0%)		1/252 (0.4%)
Arthropod bite	1/257 (0.4%)		0/252 (0%)
Foot fracture	1/257 (0.4%)		0/252 (0%)
Head injury	2/257 (0.8%)		0/252 (0%)
Ligament sprain	1/257 (0.4%)		0/252 (0%)
Limb injury	1/257 (0.4%)		1/252 (0.4%)
Soft tissue injury	1/257 (0.4%)		0/252 (0%)
Thermal burn	1/257 (0.4%)		0/252 (0%)
Investigations
Alanine aminotransferase increased	16/257 (6.2%)		8/252 (3.2%)
Alpha 1 foetoprotein increased	1/257 (0.4%)		0/252 (0%)
Amylase increased	2/257 (0.8%)		1/252 (0.4%)
Aspartate aminotransferase increased	5/257 (1.9%)		3/252 (1.2%)
Blood bilirubin increased	0/257 (0%)		1/252 (0.4%)
Blood creatine phosphokinase	1/257 (0.4%)		0/252 (0%)
Blood creatine phosphokinase increased	7/257 (2.7%)		8/252 (3.2%)
Blood glucose increased	1/257 (0.4%)		0/252 (0%)
Blood phosphorus decreased	4/257 (1.6%)		5/252 (2%)
Blood potassium decreased	1/257 (0.4%)		0/252 (0%)
Eosinophil count increased	0/257 (0%)		1/252 (0.4%)
Haemoglobin decreased	0/257 (0%)		1/252 (0.4%)
Hepatitis B DNA increased	1/257 (0.4%)		0/252 (0%)
Lymphocyte count increased	0/257 (0%)		1/252 (0.4%)
Monocyte count decreased	1/257 (0.4%)		0/252 (0%)
Neutrophil count decreased	1/257 (0.4%)		1/252 (0.4%)
Platelet count decreased	3/257 (1.2%)		2/252 (0.8%)
Prothrombin time prolonged	3/257 (1.2%)		2/252 (0.8%)
Red blood cell count decreased	0/257 (0%)		1/252 (0.4%)
Transaminases increased	1/257 (0.4%)		1/252 (0.4%)
White blood cell count decreased	1/257 (0.4%)		0/252 (0%)
White blood cell count increased	1/257 (0.4%)		0/252 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/257 (0.4%)		0/252 (0%)
Diabetes mellitus	1/257 (0.4%)		2/252 (0.8%)
Gout	0/257 (0%)		1/252 (0.4%)
Hyperuricaemia	1/257 (0.4%)		0/252 (0%)
Type 2 diabetes mellitus	1/257 (0.4%)		0/252 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/257 (0.4%)		1/252 (0.4%)
Back pain	2/257 (0.8%)		2/252 (0.8%)
Bone pain	1/257 (0.4%)		0/252 (0%)
Musculoskeletal discomfort	1/257 (0.4%)		0/252 (0%)
Musculoskeletal pain	1/257 (0.4%)		0/252 (0%)
Myalgia	0/257 (0%)		1/252 (0.4%)
Neck pain	1/257 (0.4%)		0/252 (0%)
Pain in extremity	2/257 (0.8%)		1/252 (0.4%)
Periarthritis	1/257 (0.4%)		0/252 (0%)
Spinal pain	1/257 (0.4%)		0/252 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma of liver	1/257 (0.4%)		2/252 (0.8%)
Haemangioma of spleen	0/257 (0%)		1/252 (0.4%)
Hepatic neoplasm	1/257 (0.4%)		1/252 (0.4%)
Nervous system disorders
Dizziness	2/257 (0.8%)		4/252 (1.6%)
Headache	2/257 (0.8%)		1/252 (0.4%)
Memory impairment	0/257 (0%)		1/252 (0.4%)
Poor quality sleep	0/257 (0%)		2/252 (0.8%)
Somnolence	1/257 (0.4%)		0/252 (0%)
Vascular headache	0/257 (0%)		1/252 (0.4%)
Pregnancy, puerperium and perinatal conditions
Imminent abortion	0/257 (0%)		1/252 (0.4%)
Pregnancy	0/257 (0%)		1/252 (0.4%)
Psychiatric disorders
Abnormal dreams	0/257 (0%)		1/252 (0.4%)
Insomnia	2/257 (0.8%)		4/252 (1.6%)
Sleep disorder	1/257 (0.4%)		0/252 (0%)
Renal and urinary disorders
Nephrolithiasis	5/257 (1.9%)		13/252 (5.2%)
Dysuria	0/257 (0%)		1/252 (0.4%)
Haematuria	2/257 (0.8%)		0/252 (0%)
Hydronephrosis	0/257 (0%)		2/252 (0.8%)
Nephrocalcinosis	0/257 (0%)		1/252 (0.4%)
Renal cyst	6/257 (2.3%)		3/252 (1.2%)
Renal failure	1/257 (0.4%)		0/252 (0%)
Ureterolithiasis	0/257 (0%)		2/252 (0.8%)
Reproductive system and breast disorders
Menstrual disorder	1/257 (0.4%)		0/252 (0%)
Menstruation delayed	1/257 (0.4%)		0/252 (0%)
Prostatitis	0/257 (0%)		2/252 (0.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/257 (0%)		1/252 (0.4%)
Cough	1/257 (0.4%)		3/252 (1.2%)
Dyspnoea	1/257 (0.4%)		0/252 (0%)
Nasal polyps	1/257 (0.4%)		1/252 (0.4%)
Oropharyngeal pain	1/257 (0.4%)		2/252 (0.8%)
Productive cough	0/257 (0%)		1/252 (0.4%)
Rhinitis atrophic	0/257 (0%)		1/252 (0.4%)
Skin and subcutaneous tissue disorders
Acne	1/257 (0.4%)		0/252 (0%)
Alopecia	2/257 (0.8%)		0/252 (0%)
Dermatitis atopic	0/257 (0%)		1/252 (0.4%)
Eczema	0/257 (0%)		1/252 (0.4%)
Onychomadesis	1/257 (0.4%)		0/252 (0%)
Pruritus	3/257 (1.2%)		2/252 (0.8%)
Rash	1/257 (0.4%)		1/252 (0.4%)
Surgical and medical procedures
Inguinal hernia repair	1/257 (0.4%)		0/252 (0%)
Tooth extraction	1/257 (0.4%)		0/252 (0%)
Vascular disorders
Hypertension	3/257 (1.2%)		1/252 (0.4%)
Raynaud's phenomenon	1/257 (0.4%)		0/252 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.