Treatment of Persistent Viremia (Virus in Blood) in Chronic Hepatitis B Subjects Already Receiving Adefovir Dipivoxil

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00307489
• Collaborator: (none)
• Enrollment: 106
• Locations: 28
• Arms: 2
• Duration (Months): 55
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study explores the efficacy, safety and tolerability of tenofovir DF (TDF) 300 mg once daily monotherapy versus the combination of emtricitabine 200 mg plus tenofovir DF 300 mg (FTC/TDF) once daily in subjects currently being treated with adefovir dipivoxil (Hepsera) for chronic hepatitis B who have persistent viral replication (detectable hepatitis B virus deoxyribonucleic acid [HBV DNA]).

Subjects with confirmed (within 4 weeks) plasma HBV DNA ≥ 400 copies/mL during double blind treatment at Week 24 or any time thereafter have the option of receiving 12 weeks of open-label FTC/TDF which may be continued through the end of the 168-week treatment period if there is a virologic response (HBV DNA < 400 copies/mL). Alternatively, subjects with confirmed HBV DNA < 400 copies/mL at or any time after Week 24 of double-blind treatment may continue blinded therapy up to Week 168 at the discretion of the investigator. If, in the investigator's opinion, it is felt that continued blinded treatment beyond 24 weeks in subjects with confirmed HBV DNA ≥ 400 copies/mL is not beneficial, the subject may discontinue the study and begin commercially available HBV therapy rather than initiate open-label FTC/TDF.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: tenofovir DF; Drug: emtricitabine /tenofovir DF	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind Study Exploring the Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects Currently Being Treated With Adefovir Dipivoxil for Chronic Hepatitis B and Having Persistent Viral Replication
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 TDF	Drug: tenofovir DF; 300 mg tablet, once daily (QD)
Experimental: 2 FTC/TDF	Drug: emtricitabine /tenofovir DF; emtricitabine 200 mg/tenofovir DF 300 mg once daily (combination tablet)

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48 [48 weeks]

2. Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48 [48 Weeks]

Secondary Outcome Measures

1. Change From Baseline in log10 Plasma HBV DNA Levels at Week 48 [48 Weeks]

2. Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48 [48 Weeks]

3. Percentage of Participants With Normal ALT at Week 48 [48 Weeks]

   ULN for males = 43 U/L; 34 U/L for females

4. Percentage of Participants With Normalized ALT at Week 48 [48 Weeks]

   Subjects with elevated ALT at baseline that return to normal by Week 48.

5. Hepatitis B Early Antigen (HBeAg) Loss at Week 48 [48 Weeks]

   Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.

6. HBeAg Seroconversion at Week 48 [48 Weeks]

   Defined as having negative serum HBeAg and positive serum antibody to HBeAg [anti-HBe] for subjects with positive serum HBeAg at baseline.

7. HBsAg Loss at Week 48 [48 Weeks]

   Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

8. Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48 [48 Weeks]

   Defined as having negative serum HBsAg and positive serum antibody to HBsAg [anti-HBs] for subject with positive serum HBsAg at baseline.

9. Change From Baseline in log10 Plasma HBV DNA Levels at Week 168 [168 weeks]

10. Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168 [168 weeks]

11. Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168 [168 weeks]

12. Percentage of Participants With Normal ALT at Week 168 [168 weeks]

    ULN for males = 43 U/L; ULN for females = 34 U/L

13. Percentage of Participants With Normalized ALT at Week 168 [168 weeks]

    Subjects with elevated ALT at baseline that return to normal by Week 48.

14. Hepatitis B Early Antigen (HBeAg) Loss at Week 168 [168 weeks]

    Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.

15. Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168 [168 weeks]

    Defined as having negative serum BHsAg and positive serum antibody to HBsAg (anti-HBs) for subject with positive serum BHsAg at baseline.

16. HBsAg Loss at Week 168 [168 weeks]

    Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.

17. Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168 [168 weeks]

    P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 through 69 years of age, inclusive

• Chronic HBV infection, defined as positive serum HBsAg for at least 6 months

• Active chronic HBV infection with all the following:

1. Currently treated with adefovir dipivoxil 10 mg QD (for at least 24 weeks but not more than 96 weeks)

2. HBeAg positive or negative at screening

3. Plasma HBV DNA >/= 1000 copies/mL at screening (irrespective of HBeAg status)

4. Serum ALT less than 10 times the upper limit of normal (ULN)

5. Calculated creatinine clearance of at least 70 mL/min using the Cockcroft-Gault formula

6. Hemoglobin at least 8 g/dL

7. Neutrophils at least 1,000 /mm3

• Nucleoside naive except for lamivudine (>/= 12 weeks of therapy)

• Negative serum beta human chorionic gonadotropin

• Compliant with adefovir dipivoxil

• Willing and able to provide written informed consent

Exclusion Criteria:

• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study

• Male or females of reproductive potential who are unwilling to use an effective method of contraceptive while enrolled in the study. For males, condoms should be used and for females, a barrier contraception method should be used

• Decompensated liver disease defined as conjugated bilirubin greater than 1.5 times ULN, prothrombin time (PT) greater than 1.5 times ULN, platelets less than 75,000/mm3, serum albumin less than 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)

• Prior use of tenofovir DF or entecavir

• Received treatment with interferon or pegylated interferon within 6 months of the screening visit

• Evidence of hepatocellular carcinoma (HCC); for example, alpha-fetoprotein greater than 50 ng/mL or by any other standard of care measure.

• Co-infection with HCV (based on serology), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV)

• Significant renal, cardiovascular, pulmonary, or neurological disease.

• Received solid organ or bone marrow transplantation.

• Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion

• Has proximal tubulopathy

• Known hypersensitivity to the study drugs (tenofovir DF or emtricitabine/tenofovir DF), the metabolites (tenofovir or emtricitabine) or formulation excipients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		San Francisco	California	United States	94115
2		San Jose	California	United States	95128
3		Flushing	New York	United States	11355
4		New York	New York	United States	10013
5		New York	New York	United States	10016
6		New York	New York	United States	10021
7		Philadelphia	Pennsylvania	United States	19107
8		Fairfax	Virginia	United States	22031
9		Norfolk	Virginia	United States	23502
10		Richmond	Virginia	United States	23249
11		Angers		France	49933
12		Clichy		France	92110
13		Lille		France	59037
14		Lyon		France	69288
15		Marseille		France	13285
16		Rouen		France	76031
17		Strasbourg		France	67091
18		Berlin		Germany	10969
19		Berlin		Germany	13353
20		Bonn		Germany	53105
21		Erlangen		Germany	91054
22		Essen		Germany	45122
23		Frankfurt		Germany	60590
24		Hamburg		Germany	20999
25		Hannover		Germany	30623
26		Herne		Germany	44623
27		Munchen		Germany	81377
28		Sevilla		Spain	41014

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Stephen J Rossi, PharmD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00307489
• Other Study ID Numbers: GS-US-174-0106
• First Posted: Mar 28, 2006
• Last Update Posted: Nov 1, 2011
• Last Verified: Oct 1, 2011

• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Tenofovir; Emtricitabine

Study Results

Participant Flow

Recruitment Details	A total of 106 subjects were randomized (105 of which were subsequently treated) across 28 study centers in the US, Germany, France and Spain between 24 April 2006 and 07 March 2007.

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Period Title: Baseline Through Week 48
STARTED	53	52
COMPLETED	52	50
NOT COMPLETED	1	2
Period Title: Baseline Through Week 48
STARTED	52	50
COMPLETED	46	44
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF	Total
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)	Total of all reporting groups
Overall Participants	53	52	105
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (11.4)	39 (10.4)	39 (10.9)
Sex: Female, Male (Count of Participants)
Female	15 28.3%	10 19.2%	25 23.8%
Male	38 71.7%	42 80.8%	80 76.2%
Race/Ethnicity, Customized (Number) [Number]
Asian	26 49.1%	18 34.6%	44 41.9%
Black or African American	2 3.8%	8 15.4%	10 9.5%
White	23 43.4%	21 40.4%	44 41.9%
Other	2 3.8%	5 9.6%	7 6.7%
Previous Lamivudine Experience (participants) [Number]
Yes	30 56.6%	31 59.6%	61 58.1%
No	23 43.4%	21 40.4%	44 41.9%
Baseline HBV DNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	6.06 (1.430)	5.87 (1.779)	5.97 (1.607)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 48
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

Randomized and Treated (RAT) subjects at Week 48 - Non-Completers=Failure (ie, includes subjects who switched to open-label FTC/TDF at or after Week 24)

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	52
Number [percentage of participants]	75.5 142.5%	69.2 133.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.544
	Comments	P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Change From Baseline in log10 Plasma HBV DNA Levels at Week 48
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	52	50
Mean (Standard Deviation) [log10 copies/mL]	-3.58 (1.290)	-3.34 (1.753)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	van Elteren
	Comments

3. Secondary Outcome

Title	Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 48
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	50	50
Mean (Standard Deviation) [U/mL]	-21.6 (54.53)	-41.4 (151.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.712
	Comments	Controlling for baseline HBeAg and prior lamivudine use.
	Method	van Elteren
	Comments

4. Primary Outcome

Title	Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 48
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	52
Number [percentage of participants]	81.1 153%	80.8 155.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.988
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Normal ALT at Week 48
Description	ULN for males = 43 U/L; 34 U/L for females
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	51	52
Number [percentage of participants]	66.7 125.8%	73.1 140.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.423
	Comments	Controlling for baseline HBeAg status and prior lamivudine use
	Method	Cochran-Mantel-Haenszel
	Comments

6. Secondary Outcome

Title	Percentage of Participants With Normalized ALT at Week 48
Description	Subjects with elevated ALT at baseline that return to normal by Week 48.
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set - subjects with ALT above ULN at baseline. Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	27	26
Number [percentage of participants]	40.7 76.8%	61.5 118.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Hepatitis B Early Antigen (HBeAg) Loss at Week 48
Description	Defined as having negative serum HBeAg for subjects with positive HBeAg at baseline.
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set with Positive HBeAg at Baseline. Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	38	39
Number [participants]	3 5.7%	3 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.952
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Controlling for baseline HBeAg and prior lamivudine use.

8. Secondary Outcome

Title	HBeAg Seroconversion at Week 48
Description	Defined as having negative serum HBeAg and positive serum antibody to HBeAg [anti-HBe] for subjects with positive serum HBeAg at baseline.
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set with Positive Baseline HBeAg. Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	38	39
Number [participants]	2 3.8%	3 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.655
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

9. Secondary Outcome

Title	HBsAg Loss at Week 48
Description	Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	51
Number [participants]	1 1.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 48
Description	Defined as having negative serum HBsAg and positive serum antibody to HBsAg [anti-HBs] for subject with positive serum HBsAg at baseline.
Time Frame	48 Weeks

Outcome Measure Data

Analysis Population Description

RAT Analysis Set Non-Completers=Failure

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	51
Number [participants]	1 1.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

11. Secondary Outcome

Title	Change From Baseline in log10 Plasma HBV DNA Levels at Week 168
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completers = failure analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	52
Mean (Standard Deviation) [log10 copies/mL]	-3.79 (1.305)	-3.48 (1.629)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.103
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	van Elteren
	Comments

12. Secondary Outcome

Title	Change From Baseline in Alanine Aminotransferase (ALT) Levels at Week 168
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completers = failure analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	52
Mean (Standard Deviation) [U/mL]	-26.8 (60.23)	-54.5 (141.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	van Elteren
	Comments

13. Secondary Outcome

Title	Percentage of Participants With Plasma HBV DNA < 400 Copies/mL at Week 168
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completers = failure analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	53	52
Number [Percent of Participants]	82.4 155.5%	84.0 161.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.781
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

14. Secondary Outcome

Title	Percentage of Participants With Normal ALT at Week 168
Description	ULN for males = 43 U/L; ULN for females = 34 U/L
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completers = failure analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	50	50
Number [Percent of Participants]	74.0 139.6%	74.0 142.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.936
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

15. Secondary Outcome

Title	Percentage of Participants With Normalized ALT at Week 168
Description	Subjects with elevated ALT at baseline that return to normal by Week 48.
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	25	24
Number [Percent of Participants]	68.0 128.3%	70.8 136.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.784
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

16. Secondary Outcome

Title	Hepatitis B Early Antigen (HBeAg) Loss at Week 168
Description	Defined as having negative serum HBeAg for subjecst with positive HBeAg at baseline.
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completer = Failure Analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	37	37
Number [Percent of Participants]	21.6 40.8%	24.3 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.703
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

17. Secondary Outcome

Title	Hepatitis B Surface Antigen (HBsAg) Seroconversion at Week 168
Description	Defined as having negative serum BHsAg and positive serum antibody to HBsAg (anti-HBs) for subject with positive serum BHsAg at baseline.
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completer = Failure Analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	51	51
Number [Participants]	1 1.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

18. Secondary Outcome

Title	HBsAg Loss at Week 168
Description	Defined as having negative serum HBsAg for subjects with positive HBsAg at baseline.
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	51	51
Number [Participants]	1 1.9%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments	Controlling for baseline HBeAg status and prior lamivudine use.
	Method	Cochran-Mantel-Haenszel
	Comments

19. Secondary Outcome

Title	Percentage of Participants With Plasma HBV DNA < 169 Copies/mL at Week 168
Description	P-values were from a Cochran-Mantel-Haenszel test, controlling for baseline HBeAg status and prior lamivudine use.
Time Frame	168 weeks

Outcome Measure Data

Analysis Population Description

Non-completers = failure analysis

Arm/Group Title	Tenofovir DF	Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD	emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
Measure Participants	51	50
Number [Percent of Participants]	80.4 151.7%	78.0 150%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tenofovir DF, Emtricitibine/Tenofovir DF
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.878
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	168 weeks
Arm/Group Title	Tenofovir DF		Emtricitibine/Tenofovir DF
Arm/Group Description	tenofovir DF 300 mg QD		emtricitabine 200 mg / tenofovir DF 300 mg QD (combination tablet)
All Cause Mortality
	Tenofovir DF		Emtricitibine/Tenofovir DF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tenofovir DF		Emtricitibine/Tenofovir DF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/ (NaN)		10/ (NaN)
Blood and lymphatic system disorders
Anaemia	1/53 (1.9%)		0/52 (0%)
Cardiac disorders
Atrial Fibrillation	0/53 (0%)		1/52 (1.9%)
Gastrointestinal disorders
Colitis ulcerative	1/53 (1.9%)		0/52 (0%)
General disorders
Chest Pain	1/53 (1.9%)		0/52 (0%)
Oedema Peripheral	1/53 (1.9%)		0/52 (0%)
Infections and infestations
Appendicitis	0/53 (0%)		1/52 (1.9%)
Chronic Sinusitis	0/53 (0%)		1/52 (1.9%)
Gastroenteritis	1/53 (1.9%)		0/52 (0%)
Sepsis	0/53 (0%)		1/52 (1.9%)
Investigations
Alanine Aminotransferase Increased	0/53 (0%)		2/52 (3.8%)
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion	0/53 (0%)		1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of Breast	0/53 (0%)		1/52 (1.9%)
Lymphoma	0/53 (0%)		1/52 (1.9%)
Waldenstrom's Macroglobulinaemia	1/53 (1.9%)		0/52 (0%)
Nervous system disorders
Carotid Arteriosclerosis	1/53 (1.9%)		0/52 (0%)
Cerebrovascular Accident	0/53 (0%)		1/52 (1.9%)
Hemiparesis	0/53 (0%)		1/52 (1.9%)
Pain	0/53 (0%)		1/52 (1.9%)
Psychiatric disorders
Alcoholism	0/53 (0%)		1/52 (1.9%)
Renal and urinary disorders
Renal failure	0/53 (0%)		1/52 (1.9%)
Reproductive system and breast disorders
Bartholinitis	0/53 (0%)		1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/53 (1.9%)		0/52 (0%)
Respiratory failure	0/53 (0%)		1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Tenofovir DF		Emtricitibine/Tenofovir DF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/ (NaN)		42/ (NaN)
Blood and lymphatic system disorders
Anaemia	3/53 (5.7%)		1/52 (1.9%)
Gastrointestinal disorders
Abdominal Pain	5/53 (9.4%)		5/52 (9.6%)
Abdominal Pain Upper	8/53 (15.1%)		9/52 (17.3%)
Constipation	2/53 (3.8%)		3/52 (5.8%)
Diarrhoea	5/53 (9.4%)		3/52 (5.8%)
Dyspepsia	4/53 (7.5%)		2/52 (3.8%)
Haemorrhoids	3/53 (5.7%)		1/52 (1.9%)
Nausea	5/53 (9.4%)		2/52 (3.8%)
Gastroenteritis	3/53 (5.7%)		1/52 (1.9%)
General disorders
Asthenia	7/53 (13.2%)		2/52 (3.8%)
Fatigue	9/53 (17%)		9/52 (17.3%)
Immune system disorders
Seasonal allergy	2/53 (3.8%)		3/52 (5.8%)
Infections and infestations
Bronchitis	3/53 (5.7%)		7/52 (13.5%)
Influenza	3/53 (5.7%)		1/52 (1.9%)
Nasopharyngitis	16/53 (30.2%)		12/52 (23.1%)
Upper respiratory tract infection	1/53 (1.9%)		3/52 (5.8%)
Urinary Tract Infection	5/53 (9.4%)		4/52 (7.7%)
Investigations
Blood Creatine Phosphokinase Increased	0/53 (0%)		4/52 (7.7%)
Alanine Aminotransferase Increased	0/53 (0%)		3/52 (5.8%)
Metabolism and nutrition disorders
Decreased appetite	3/53 (5.7%)		1/52 (1.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/53 (3.8%)		5/52 (9.6%)
Back Pain	9/53 (17%)		6/52 (11.5%)
Myalgia	3/53 (5.7%)		1/52 (1.9%)
Pain in Extremity	2/53 (3.8%)		4/52 (7.7%)
Nervous system disorders
Dizziness	4/53 (7.5%)		4/52 (7.7%)
Headache	15/53 (28.3%)		10/52 (19.2%)
Paraesthesia	0/53 (0%)		3/52 (5.8%)
Psychiatric disorders
Depression	1/53 (1.9%)		3/52 (5.8%)
Insomnia	1/53 (1.9%)		3/52 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/53 (5.7%)		1/52 (1.9%)
Pharyngolaryngeal Pain	8/53 (15.1%)		3/52 (5.8%)
Skin and subcutaneous tissue disorders
Alopecia	3/53 (5.7%)		1/52 (1.9%)
Pruritis	3/53 (5.7%)		2/52 (3.8%)

Limitations/Caveats

The randomized and treated (RAT) analysis set includes all subjects who were ongoing at the time of analysis (i.e., those on blinded therapy and those who switched to open-label FTC/TDFdue to persistent viremia).

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.