Entecavir Plus Adefovir Combination Therapy Versus Enteca... | NCT00410202

Label	Type	Description	Intervention Names
Entecavir	Active Comparator	With the option of adding tenofovir at week 48. (This does not apply to Korea)	Drug: Entecavir Drug: Tenofovir
Adefovir + Lamivudine	Active Comparator		Drug: Adefovir Drug: Lamivudine
Entecavir + Adefovir	Active Comparator		Drug: Entecavir Drug: Adefovir

Name	Type	Description	Arm Group Labels	Other Names
Entecavir	Drug	Tablets, Oral, 1mg, once daily, 100 weeks	Entecavir Entecavir + Adefovir

Measure	Description	Time Frame
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48	HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.	Week 48

Measure	Description	Time Frame
Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96	HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA < 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.	Week 96

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University Of Connecticut Health Center		Farmington	Connecticut	06030	United States
Local Institution

ID	Title	Description
FG000	Entecavir + Adefovir (ETV+ADV) Combination Therapy	ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks
FG001	Entecavir (ETV) Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 50 IU/mL (Approximately 300 Copies/mL) by Polymerase Chain Reaction (PCR) at Week 48

HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants	OG000138 OG001140 OG002137

Title

Denominators

Categories

Title	Measurements
	OG00025.4 OG00116.4 OG00219.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Hochberg procedure		0.1336		Difference Estimate	8.9			2-Sided	95	-2.0	19.9				No	Superiority or Other
OG000 OG002		Hochberg procedure		0.2619

Secondary

Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at Week 96

HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. HBV DNA < 50 IU/mL = approximately 300 copies/mL. Percentage n/N: n= number of participants with HBV DNA <50 IU/mL; N = number of participants analyzed.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

Percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units

Secondary

Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48

HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Percentage n/N: n= number of participants with outcome result; N = number of participants analyzed.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Secondary

Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 96

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

Percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Secondary

Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 48

HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Secondary

Percentage of Participants Who Achieve HBV DNA < Lower Limit of Detection (LOD = 10 IU/mL [Approximately 58 Copies/mL]) at Week 96

HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay. LOD is the lowest amount or concentration of analyte in a sample, which can be reliably detected, but not necessarily quantified.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units

Secondary

Percentage of Participants With HBV DNA by PCR Category at Week 48

HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay.

Participants who received at least 1 dose of study therapy.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With HBV DNA by PCR Category at Week 96

HBV DNA assessments were performed using the Roche COBAS® TaqMan HPS assay.

Participants who received at least 1 dose of study therapy were analyzed.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Change in Mean log10 From Baseline in HBV DNA at Week 48

HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load, negative values means reduction.

Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values. n=participants with baseline and Week 48 values.

Posted

Mean

Standard Error

log10 (IU/mL

Baseline, Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Change in Mean log10 From Baseline in HBV DNA at Week 96

HBV DNA was analyzed by PCR, using the Roche COBAS® TaqMan HPS assay. Reduction in log10 HBV count=reduced viral load.

Participants who received at least 1 dose of study therapy and had both baseline and post-baseline values were analyzed. n= participants with baseline and Week 96 values.

Posted

Mean

Standard Error

participants

Baseline, Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 48

ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 or 48 U/L.

Participants who received at least 1 dose of study therapy and had ALT > 1 x ULN at baseline (day 1). Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units

Secondary

Percentage of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieve ALT Normalization at Week 96

ALT normalization=ALT level being less than or equal to 1 times the upper limit of normal (ULN). ULN for ALT is 37 U/L.

Participants who received at least 1 dose of study therapy and had ALT > 1 x ULN at baseline (day 1) were analyzed. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Baseline, Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units

Secondary

Percentage of Participants With Confirmed HBeAg Loss at Week 48 (Treated HBeAg Positive Participants Only)

HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week

Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With Confirmed HBeAg Loss at Week 96 (Treated HBeAg Positive Participants Only)

HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week

Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With HBeAg Seroconversion at Week 48 (Treated HBeAg-positive Participants Only)

HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).

Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Percentage of Participants With HBeAg Seroconversion at Week 96 (Treated HBeAg-positive Participants Only)

HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).

Participants who received at least 1 dose of study therapy and were HBeAG positive. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48

HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 96

HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.

Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Percentage of Participants With HBsAg Seroconversion at Week 48

HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.

Participants who received at least 1 dose of study therapy. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 48

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With HBsAg Seroconversion at Week 96

HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.

Participants who received at least 1 dose of study therapy were analyzed. Participants with missing efficacy assessments were considered as a failure.

Posted

Number

percentage of participants

Week 96

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts

Secondary

Cumulative Probability of Emergent Genotypic Resistance at Year 1

yr=year. Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).

Treated participants who were tested for resistance, ie. met the following selection criteria. 1) participants with HBV DNA ≥ 50 IU/mL at Week 48 or at the last on-treatment visit and 2) who developed VBT . n=participants

Posted

Number

percentage of participants

Year 1

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.

Secondary

Cumulative Probability of Emergent Genotypic Resistance at Year 2

Cumulative probability (CP): Ptotal=1-(1-Pyr1)*(1-Pyr2) where Pyear(i)= number of participants with events at Year i divided by number of participants at risk at Year i for i = 1,2. An "event" is defined as resistance or resistance with virologic breakthrough in a yearly interval. Participants 'at risk' are those who were treated during Year i and did not develop that resistance or resistance with virologic breakthrough prior to Year i. CP were calculated separately for ETV, ADV and TDF resistance. Participants who discontinue from study drug in Year i were assumed to be in follow up for the entire year. (VBT; a ≥ 1 log10 increase in HBV DNA from the on-treatment nadir, confirmed by 2 sequential HBV DNA results or observed at the last on-treatment HBV DNA). ETVr = ETV resistance (rtM204V/I/S plus any substitution at rtT184, rtS202, or rtM250); ADVr/TDFr = ADV/TDF resistance (rtA181T/V or rtN236T = ADVr and TDFr, rtA194T = TDFr only).

Treated participants who were tested for resistance were analyzed, ie. They met the following selection criteria: 1) participants with HBV DNA ≥ 50 IU/mL at Week 96 or at the last on-treatment visit and 2) who developed VBT. n=participants

Posted

Number

percentage of participants

Year 2

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.

Secondary

Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations Due to Adverse Events or Laboratory Abnormalities During Treatment

AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. Grade 1 = mild, Grade 2= moderate, Grade 3 = severe, Grade 4 = life threatening/disabling, Grade 5 = death.

All treated participants.

Posted

Number

participants

From start of study therapy through Week 100 + 5 days

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Secondary

Number of Participants With Laboratory Abnormalities: Hematology

Criteria for hematology abnormalities were: Hemoglobin: <=11.0 g/dL; White Blood Cells: <4000/mm^3; Absolute Neutrophils (includes absolute bands): <1500/mm^3; Platelets: <=99,000/mm^3; International Normalized Ratio: ≥ 1.5 and ≥ 0.5 from baseline.

All treated participants.

Posted

Number

participants

From start of study through Week 100 + 5 days

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks

Units	Counts
Participants

Secondary

Number of Participants With Laboratory Abnormalities: Serum Chemistry

ULN=upper limit of normal (Normal ranges are Central lab data and vary according to the site). ALT:>1.25*ULN, AST:>1.25*ULN, ALP:>1.25*ULN, Total Bilirubin:>1.1*ULN, Serum Lipase:>1.10*ULN, Creatinine:>1.1*ULN, Blood Urea Nitrogen:1.25*ULN, Hyperglycemia:>116 mg/dL, Hypoglycemia:<64 mg/dL, Hyponatremia:<132meq/L, Hypokalemia:<3.4 meq/L, Albumin:≥1g/dL decrease from baseline, <3 g/dL; Hypernatremia:>148 meq/L, Hyperkalemia:>5.6 meq/L, Hypokalemia:<3.4 meq/L, Hyperchloremia:>113 meq/L, Hypochloremia:<93 meq/L; ALT flare: on treatment (OT), >2*Baseline and >10*ULN; off treatment (OF), 2*end of dosing value and >10*ULN

All treated participants. n = number of participants in the OF period.

Posted

Number

participants

On treatment : Day 1 through Week 100 + 5 days; Offtreatment = End of OT period through 24 weeks

ID	Title	Description
OG000	ETV+ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; QD for 100 weeks
OG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
OG002	ADV+LVD Combination Therapy

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0022 affected138 at risk
Intracranial hypotension	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Melaena	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Pelvic infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Suicide attempt	Psychiatric disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Ureteric stenosis	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Dizziness	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0013 affected140 at risk EG0021 affected138 at risk
Plasmacytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Appendicitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0012 affected140 at risk EG0021 affected138 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0011 affected140 at risk EG0021 affected138 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Hepatitis B	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Meningitis tuberculous	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Optic atrophy	Eye disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Pyrexia	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Anal fistula	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Erosive oesophagitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Hepatic neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0002 affected137 at risk EG0015 affected140 at risk EG0024 affected138 at risk
Hydrocephalus	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Hot flush	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Tonsillitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Aneurysm ruptured	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Congenital cystic kidney disease	Congenital, familial and genetic disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0010 affected140 at risk EG0020 affected138 at risk
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0011 affected140 at risk EG0020 affected138 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected137 at risk EG0010 affected140 at risk EG0021 affected138 at risk

ID	Term
D006509	Hepatitis B
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C413685	entecavir
D000068698	Tenofovir
C053001	adefovir
C106812	adefovir dipivoxil
D019259	Lamivudine

ID	Term
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D016047	Zalcitabine
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D015224	Dideoxynucleosides

ID	Title	Description
BG000	Entecavir + Adefovir (ETV+ADV) Combination Therapy	ETV 1.0 mg + ADV 10 mg; Combination therapy given once daily (QD) for 100 weeks
BG001	Entecavir (ETV) Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.
BG002	Adefovir + Lamivudine (ADV+LVD) Combination Therapy	ADV 10 mg + LVD 100 mg; Combination therapy given QD for 100 weeks
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ADV + LVD Combination Therapy	ADV 10 mg + LVD 100 mg; QD for 100 weeks	13	137	62	137
EG001	ETV Monotherapy	ETV 1.0 mg; QD, for 100 weeks with an option of adding non-study tenofovir (TDF) at Week 48 at the investigator's discretion, and where permitted by the local health authorities and ethics committees.	21	140	75	140
EG002	ETV + ADV Combination Therapy	ETV 1.0 mg + ADV 10 mg; once daily (QD) for 100 weeks	14	138	63	138

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hepatic steatosis	Hepatobiliary disorders	MedDRA 15.0	Systematic Assessment	EG0009 affected137 at risk EG0018 affected140 at risk EG0024 affected138 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0001 affected137 at risk EG0017 affected140 at risk EG0025 affected138 at risk
Headache	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG00013 affected137 at risk EG0015 affected140 at risk EG0028 affected138 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG00019 affected137 at risk EG00128 affected140 at risk EG00223 affected138 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0006 affected137 at risk EG00110 affected140 at risk EG0025 affected138 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0003 affected137 at risk EG0017 affected140 at risk EG0022 affected138 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0007 affected137 at risk EG0013 affected140 at risk EG0028 affected138 at risk
Alanine aminotransferase increased	Investigations	MedDRA 15.0	Systematic Assessment	EG0005 affected137 at risk EG0018 affected140 at risk EG0028 affected138 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0004 affected137 at risk EG0018 affected140 at risk EG0026 affected138 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0008 affected137 at risk EG0016 affected140 at risk EG00210 affected138 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0007 affected137 at risk EG0015 affected140 at risk EG0022 affected138 at risk
Fatigue	General disorders	MedDRA 15.0	Systematic Assessment	EG0008 affected137 at risk EG0014 affected140 at risk EG0024 affected138 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0008 affected137 at risk EG00117 affected140 at risk EG00217 affected138 at risk