Trial Outcomes & Findings for Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue (NCT NCT01480284)

NCT ID: NCT01480284

Last Updated: 2016-08-10

Results Overview

The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24 was assessed (lower limit of quantitation : 2.1 log 10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 166 participants
• Primary outcome timeframe: Baseline and Week 24
• Results posted on: 2016-08-10

Participant Flow

A total of 166 participants (110 participants in the Tenofovir Disoproxil Fumarate [GSK548470, TDF] group and 56 participants in the Entecavir Hydrate [ETV] group) were enrolled in the study.

Participant milestones

Measure	TDF 300 mg OD Participants received Tenofovir Disoproxil Fumarate (TDF) 300 milligrams (mg) tablet once daily (OD) and Entecavir Hydrate (ETV) placebo capsule OD for 96 weeks.	ETV 0.5 mg OD Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Overall Study STARTED	110	56
Overall Study COMPLETED	102	56
Overall Study NOT COMPLETED	8	0

Reasons for withdrawal

Measure	TDF 300 mg OD Participants received Tenofovir Disoproxil Fumarate (TDF) 300 milligrams (mg) tablet once daily (OD) and Entecavir Hydrate (ETV) placebo capsule OD for 96 weeks.	ETV 0.5 mg OD Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	1	0
Overall Study Study closed/terminated	3	0
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	1	0

Baseline Characteristics

Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue

Baseline characteristics by cohort

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.	Total n=165 Participants Total of all reporting groups
Age, Continuous	45.4 Years STANDARD_DEVIATION 9.23 • n=93 Participants	46.1 Years STANDARD_DEVIATION 9.68 • n=4 Participants	45.6 Years STANDARD_DEVIATION 9.36 • n=27 Participants
Sex: Female, Male Female	41 Participants n=93 Participants	16 Participants n=4 Participants	57 Participants n=27 Participants
Sex: Female, Male Male	68 Participants n=93 Participants	40 Participants n=4 Participants	108 Participants n=27 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	109 Participants n=93 Participants	56 Participants n=4 Participants	165 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Per Protocol Set (PPS) Population: all participants who received at least 1 dose of investigational product (IP) and had at least one efficacy assessment after the treatment initiation, and with no major protocol violations. Missing values observed during the treatment period were imputed by the last observation carried forward (LOCF) method.

The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24 was assessed (lower limit of quantitation : 2.1 log 10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Measure	TDF 300 mg OD n=106 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=53 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Mean Change From Baseline in Serum HBV DNA Level at Week 24	-4.63 log10 copies/milliliter (copies/mL) Standard Error 0.044	-4.50 log10 copies/milliliter (copies/mL) Standard Error 0.063

SECONDARY outcome

Timeframe: Baseline, Week 48 and Week 96

Population: Full Analysis Set (FAS) Population: all participants who entered into the study, received at least one dose of investigational product, and have at least one efficacy assessment after the treatment initiation.

The mean change from Baseline in the HBV DNA level at Week 48 and Week 96 were assessed (lower limit of quantitation : 2.1 log10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-baseline value minus the Baseline value. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96 Week 48	-4.86 log10 copies/mL Standard Deviation 1.353	-4.85 log10 copies/mL Standard Deviation 0.916
Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96 Week 96	-4.96 log10 copies/mL Standard Deviation 1.445	NA log10 copies/mL Standard Deviation NA Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: FAS Population

The number of participants with serum HBV DNA level less than the lower limit of quantitation (i.e. 2.1 log10 copies/mL) at Week 24, Week 48 and Week 96 were summarized. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96 Week 24	59 Participants	22 Participants
Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96 Week 48	84 Participants	37 Participants
Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96 Week 96	97 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: Biochemically Evaluable Population (BEP): all participants who received at least one dose of IP and with an abnormal ALT at Baseline. The population for the analysis of ALT normalization was all participants with an ALT value \> ULN at Baseline.

The number of participants with alanine aminotransferase (ALT) normalization at Week 24, Week 48 and Week 96 were summarized. ALT normalization is defined as when an ALT value exceeds the upper limit of normal range (ULN) at Baseline and within the normal range at the end of treatment. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=83 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=41 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96 Week 24	58 Participants	35 Participants
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96 Week 48	62 Participants	35 Participants
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96 Week 96	74 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: FAS Population. Only participants with positive HBeAg at Baseline were analyzed.

The number of participants achieving hepatitis Be antigen (HBeAg) loss at Week 24, Week 48 and Week 96 in positive HBeAg participants at Baseline were summarized. Loss of HBeAg is defined as the change of detectable HBeAg from positive to negative. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=51 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=28 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96 Week 24	3 Participants	2 Participants
Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96 Week 48	9 Participants	3 Participants
Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96 Week 96	13 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: FAS Population. Only participants with positive HBeAg and negative HBeAb at Baseline were analyzed.

The number of participants achieving HBeAg/hepatitis Be antibody (HBeAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBeAg and negative HBeAb participants at Baseline were summarized. Seroconversion to HBeAg is defined as the change of detectable antibody to HBeAg from negative to positive. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=43 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=27 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96 Week 24	0 Participants	1 Participants
Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96 Week 48	4 Participants	2 Participants
Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96 Week 96	5 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: FAS Population.

The number of participants with hepatitis B surface antigen (HBsAg) loss at Week 24, Week 48 and Week 96 in positive HBsAg participants at Baseline were summarized. Loss of HBsAg is defined as change of detectable HBsAg from positive to negative. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96 Week 24	0 Participants	0 Participants
Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96 Week 48	0 Participants	0 Participants
Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96 Week 96	1 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Week 24, Week 48 and Week 96

Population: FAS Population. Only participants with positive HBsAg and negative HBsAb at Baseline were analyzed.

The number of participants with HBsAg/hepatitis B surface antibody (HBsAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBsAg and negative HBsAb participants at Baseline were summarized. HBsAg seroconversion .is defined as change of detectable antibody to HBsAg from negative to positive. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=104 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=53 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96 Week 24	0 Participants	0 Participants
Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96 Week 48	0 Participants	0 Participants
Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96 Week 96	1 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48 and Week 96

Population: FAS Population

The number of participants achieving each indicated HBsAg category (HBsAg <80, 80 to 800, 800 to 8000, 8000 to 80000, and >=80000) (kilo international unit per liter [KIU/L]) by study visit was summarized. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg <80 KIU/L, Baseline	2 Participants	2 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 80-800 KIU/L, Baseline	15 Participants	10 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 800-8000 KIU/L, Baseline	58 Participants	33 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 8000-80,000 KIU/L, Baseline	31 Participants	10 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg >=80,000 KIU/L, Baseline	3 Participants	1 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg <80 KIU/L, Week 24	3 Participants	1 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 80-800 KIU/L, Week 24	17 Participants	10 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 800-8000 KIU/L, Week 24	63 Participants	36 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 8000-80,000 KIU/L, Week 24	26 Participants	9 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg >=80,000 KIU/L, Week 24	0 Participants	0 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg <80 KIU/L, Week 48	5 Participants	1 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 80-800 KIU/L, Week 48	19 Participants	9 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 800-8000 KIU/L, Week 48	60 Participants	39 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 8000-80,000 KIU/L, Week 48	25 Participants	7 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg >=80,000 KIU/L, Week 48	0 Participants	0 Participants
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg <80 KIU/L, Week 96	5 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 80-800 KIU/L, Week 96	23 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 800-8000 KIU/L, Week 96	60 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg 8000-80,000 KIU/L, Week 96	21 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 HBsAg >=80,000 KIU/L, Week 96	0 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: Baseline, Week 24, Week 48 and Week 96

Population: FAS Population

The number of participants achieving each indicated hepatitis B core-related antigen (HBcrAg) category (HBcrAg <3.0, 3.0 to 4.0, 4.0 to 5.0, 5.0 to 6.0, and >=6.0) (Log kilo unit per liter [KU/L]) by study visit was summarized. The LOCF method was applied for missing values.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg <3.0 Log KU/L, Week 96	24 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 3.0-4.0 Log KU/L, Week 96	18 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg <3.0 Log KU/L, Baseline	7 Participants	0 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 3.0-4.0 Log KU/L, Baseline	13 Participants	6 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 4.0-5.0 Log KU/L, Baseline	19 Participants	11 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 5.0-6.0 Log KU/L, Baseline	19 Participants	9 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg >=6.0 Log KU/L, Baseline	51 Participants	30 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg <3.0 Log KU/L, Week 24	21 Participants	10 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 3.0-4.0 Log KU/L, Week 24	16 Participants	8 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 4.0-5.0 Log KU/L, Week 24	18 Participants	8 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 5.0-6.0 Log KU/L, Week 24	17 Participants	7 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg >=6.0 Log KU/L, Week 24	37 Participants	23 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg <3.0 Log KU/L, Week 48	24 Participants	12 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 3.0-4.0 Log KU/L, Week 48	16 Participants	6 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 4.0-5.0 Log KU/L, Week 48	18 Participants	9 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 5.0-6.0 Log KU/L, Week 48	23 Participants	10 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg >=6.0 Log KU/L, Week 48	28 Participants	19 Participants
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 4.0-5.0 Log KU/L, Week 96	22 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg 5.0-6.0 Log KU/L, Week 96	23 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 HBcrAg >=6.0 Log KU/L, Week 96	22 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.

SECONDARY outcome

Timeframe: From Baseline to throughout study

Population: FAS Population

The number of participants who experienced virological breakthrough was summarized. Virological breakthrough is defined as serum HBV DNA level increase >=1 log10 copies/mL above the treatment nadir. Virological breakthrough values were presented from Baseline to through out the study. Baseline is defined as the value at Week 0 visit.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With Virological Breakthrough Through End of the Study	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study)

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

The development of drug resistance-related (RA) mutations was analyzed to look for resistance to Lamivudine (LAM), Adefovir dipivoxil (ADV), and/or ETV in a case where a virologic breakthrough has been observed after starting the study treatment (serum HBV DNA level has increased from the nadir by at least 1 log10 copies/mL) or where the serum HBV DNA level is not less than the HBV DNA detection limit (2.1 log10 copies/mL) at Week 24, Week 48 and Week 96. Virologic breakthrough was defined as 1.0 log10 or greater increases in serum HBV-DNA levels from on-treatment nadir. Participants who achieved the HBV-DNA values below lower limit of quantification (LLQ) (< 2.1 log10 copies/mL) in quantitative analysis at entire the study were also considered "Negative" in drug-resistance without implementation of genotypic analysis. Resistance mutation values were presented from Baseline to throughout the study. Baseline is defined as the value at Week 0 visit.

Outcome measures

Measure	TDF 300 mg OD n=109 Participants Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 Participants Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) LAM RA mutations, Screening, n=109, 56	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ADV RA mutations, Screening, n=109, 56	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ETV RA mutations, Screening, n=109, 56	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) LAM RA mutations, Week 24, n=49, 34	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ADV RA mutations, Week 24, n=49, 34	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ETV RA mutations, Week 24, n=49, 34	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) LAM RA mutations, Week 48, n=23, 19	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ADV RA mutations, Week 48, n=23, 19	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ETV RA mutations, Week 48, n=23, 19	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) LAM RA mutations, Week 96, n=11, 0	0 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ADV RA mutations, Week 96, n=11, 0	0 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ETV RA mutations, Week 96, n=11, 0	0 Participants	NA Participants Participants assigned to the arm ETV 0.5 mg OD completed the study at Week 48; therefore, there are no results for Week 96.
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) LAM RA mutations, Virologic Breakthrough, n=2, 2	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ADV RA mutations, Virologic Breakthrough, n=2, 2	0 Participants	0 Participants
Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) ETV RA mutations, Virologic Breakthrough, n=2, 2	0 Participants	0 Participants

Adverse Events

TDF 300 mg OD

Serious events: 7 serious events

Other events: 83 other events

Deaths: 0 deaths

ETV 0.5 mg OD

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Measure	TDF 300 mg OD n=109 participants at risk Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 participants at risk Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Cardiac disorders Arrhythmia	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Food poisoning	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Urinary tract infection	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.8% 2/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Large intestine polyp	0.00% 0/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	1.8% 1/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Nervous system disorders Dizziness	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Injury, poisoning and procedural complications Multiple fractures	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	1.8% 1/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.

Other adverse events

Measure	TDF 300 mg OD n=109 participants at risk Participants received TDF 300 mg tablet OD and ETV placebo capsule OD for 96 weeks.	ETV 0.5 mg OD n=56 participants at risk Participants received ETV 0.5 mg capsule OD and TDF placebo tablet OD for 48 weeks.
Infections and infestations Nasopharyngitis	44.0% 48/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	42.9% 24/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Nervous system disorders Headache	14.7% 16/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	8.9% 5/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Investigations Blood creatine phosphokinase increased	10.1% 11/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	7.1% 4/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Influenza	9.2% 10/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Pharyngitis	9.2% 10/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	3.6% 2/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Sinusitis	6.4% 7/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Infections and infestations Oral herpes	5.5% 6/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Nervous system disorders Dizziness	5.5% 6/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	3.6% 2/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Investigations Lipase increased	5.5% 6/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	3.6% 2/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain upper	7.3% 8/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	0.00% 0/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Dental caries	3.7% 4/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	7.1% 4/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Diarrhoea	4.6% 5/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Gastrointestinal disorders Constipation	2.8% 3/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Back pain	5.5% 6/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	7.1% 4/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Myalgia	3.7% 4/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Cough	6.4% 7/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	3.6% 2/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Skin and subcutaneous tissue disorders Rash	1.8% 2/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	8.9% 5/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.
Immune system disorders Seasonal allergy	0.92% 1/109 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.	5.4% 3/56 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to average of 96 weeks). SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of investigational product.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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