Effect of Entecavir in Blacks/African Americans and Hispanics With Chronic Hepatitis B Virus (HBV) Infection

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00371150
• Collaborator: (none)
• Enrollment: 131
• Locations: 27
• Arm: 1
• Duration (Months): 51.9
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to develop observational clinical experience with the use of entecavir in participants who are either of Black/African-American race or of Hispanic ethnicity.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B Infection	Drug: Entecavir	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Describe the Antiviral Effect of Entecavir (ETV) in Blacks/African Americans and Hispanics With Chronic Hepatitis B Virus (HBV) Infection Who Are Nucleoside-Naive
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm1	Drug: Entecavir; Tablets, Oral, 0.5 mg, once daily, up to 52 weeks; Other Names: Baraclude BMS-200475

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) < 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 48 [Week 48 of ETV treatment]

   HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA < 50 IU/mL = approximately <300 copies/mL.

Secondary Outcome Measures

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

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

2. Percentage of Participants With HBV DNA by PCR Category at Week 48 [Week 48]

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

3. Percentage of Participants With Virologic Rebound Through Week 48 While on Continued Dosing With ETV [through Week 48]

   Virologic rebound is defined as a confirmed increase of ≥ 1 log10 in HBV DNA from the participant's nadir value (2 sequential HBV DNA measurements or last on-treatment measurement)

4. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 [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 U/L.

5. Percentage of Participants With Confirmed HBeAg Loss at Week 48 (for HBeAg-positive Participants Only) [Week 48]

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

6. Percentage of Participants With HBeAg Seroconversion at Week 48 (for HBeAg-positive Participants Only) [Week 48]

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

7. Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48 [Week 48]

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

8. Percentage of Participants With HBsAg Seroconversion at Week 48 [Week 48]

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

9. Mean log10 Reduction From Baseline in HBV DNA at Week 48 [baseline, Week 48]

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

10. Percentage of Participants With HBV DNA < Other IU Cut-off Points That May be Clinically Relevant at the Time of Data Analysis [Week 48]

11. Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to Adverse Events [From enrollment through Week 52 + 5 days]

    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.

12. Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF): Hematology [OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up]

    Criteria for hematology abnormalities were graded using the modified WHO grading system. 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.

13. Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) : Serum Chemistry [OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up]

    The modified World Health Oranization(WHO)grading system was used to grade the abnormalities. ULN=upper limit of normal. Alanine aminotransferase:>1.25xULN, Aspartate aminotransferase:>1.25xULN, Alkaline Phosphatase:>1.25xULN, Total Bilirubin:>1.1xULN, Serum Lipase:>1.10xULN, Creatinine:>1.1xULN, Blood Urea Nitrogen:1.25xULN, 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic HBV infection, with either HBeAg-positive (HBeAb-negative) or HBeAg-negative (HBeAb-positive) disease

• Black/African American Race and/or Hispanic ethnicity

• Nucleoside/tide-naive

• Males or females ≥ 16 years of age (or minimum age required in a given country)

• Compensated liver function

• ALT of 1.3 to 10 x upper limit of normal (ULN)

• No Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV)

Exclusion Criteria

• Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 weeks after study medication has been discontinued

• Women who are pregnant or breastfeeding

• Women with a positive pregnancy test on enrollment or prior to study drug administration

• Evidence of decompensated cirrhosis including but not limited to: variceal bleeding; hepatic encephalopathy; or ascites requiring management with diuretics or paracentesis

• Recent history of pancreatitis (resolution of any recent pancreatitis must be documented by normal lipase at least 12 weeks prior to the first dose of study medication)

• Currently abusing illegal drugs or alcohol sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of hepatotoxicity or pancreatitis

• Other serious medical conditions that might preclude completion of this study or that require chronic administration of prohibited medications

• Serum creatinine > 1.5 mg/dL

• Hemoglobin < 10.0 g/dL

• Platelet count < 70,000/mm3

• Absolute neutrophil count < 1200 cells/mm3

• Serum alpha fetoprotein (AFP) level > 100 ng/mL. If the AFP level is between 21 and 100 ng/mL, it must be repeated. If the repeat AFP level is between 21 and 100 ng/mL and if ultrasonography or computerized tomography (CT) of the liver performed prior to the first dose of study medication does not demonstrate a focal lesion suggestive of carcinoma, the subject may be dosed in the study

• Known history of allergy to nucleoside analogues

• Any prior therapy with Entecavir

• Any prior or concomitant use of nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., ETV, lamivudine (LVD), tenofovir [TDF], emtricitabine (FTC), clevudine, telbivudine [LdT], famciclovir), or any other experimental anti-HBV antiviral agent

• Therapy with interferon, thymosin alpha or other immunostimulators within 24 weeks of enrollment (i.e., dosing) into this study

• Subjects who require chronic administration of concomitant medications which cause immunosuppression or which are associated with a high rate of nephrotoxicity or hepatotoxicity, or which affect renal excretion, should not be enrolled in this study

• Unable to tolerate oral medication

• Poor peripheral venous access

• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Liver & Digestive Specialists (Alds)	Montgomery	Alabama	United States	36116
2	University Of Arizona	Tucson	Arizona	United States	85724
3	George Washington University Medical Center	Washington	District of Columbia	United States	20037
4	University Of Miami	Miami	Florida	United States	33136
5	Empire International Research	Miami	Florida	United States	33144
6	University Of Chicago	Chicago	Illinois	United States	60637
7	Banks Hepatology Institute, Pc	College Park	Maryland	United States	20740
8	Brigham And Women'S Hospital	Boston	Massachusetts	United States	02115
9	L L C Bda The Research Institute	Springfield	Massachusetts	United States	01107
10	Va New York Harbor Healthcare System	New York	New York	United States	10010
11	Westchester Digestive Disease Group, Llp	Yonkers	New York	United States	10701
12	Albert Einstein Healthcare Network	Philadelphia	Pennsylvania	United States	19141
13	Alamo Medical Research	San Antonio	Texas	United States	78215
14	Hunter Holmes Mcguire D V A M C	Richmond	Virginia	United States	23249
15	Local Institution	Salvador	Bahia	Brazil	40110
16	Local Institution	Belo Horizonte - Mg	Minas Gerais	Brazil	30150
17	Local Institution	Rio De Janeiro - Rj	Rio De Janeiro	Brazil	20210
18	Local Institution	Campinas	Sao Paulo	Brazil	13083
19	Local Institution	Sao Paulo - Sp	Sao Paulo	Brazil	01246
20	Local Institution	Df	Distrito Federal	Mexico	14000
21	Local Institution	Guadalajara	Jalisco	Mexico	44270
22	Local Institution	Guadalajara	Jalisco	Mexico	44280
23	Local Institution	Guadalajara	Jalisco	Mexico	44650
24	Local Institution	Zapopan	Jalisco	Mexico	45150
25	Local Institution	Santurce		Puerto Rico	00909
26	Local Institution	Belville	Western Cape	South Africa	7350
27	Local Institution	Goodwood	Western Cape	South Africa	7460

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00371150
• Other Study ID Numbers: AI463-085
• First Posted: Sep 1, 2006
• Last Update Posted: Apr 16, 2012
• Last Verified: Mar 1, 2012

• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Entecavir

Study Results

Participant Flow

Recruitment Details	A total of 131 participants were enrolled at 27 sites.
Pre-assignment Detail	Of the 131 participants enrolled, 85 were never treated (82 no longer met study criteria, 2 withdrew consent, and 1 had other reason).

Arm/Group Title	Black/ African American	Hispanic
Arm/Group Description	Entecavir (ETV) tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks
Period Title: Overall Study
STARTED	40	6
Discontinued Prior to Week 48 Visit	1	1
Discontinued at or After Week 48 Visit	2	1
COMPLETED	37	4
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Black/ African American	Hispanic	Total
Arm/Group Description	Entecavir (ETV) tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Total of all reporting groups
Overall Participants	40	6	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39.0	48.0	40.0
Sex: Female, Male (Count of Participants)
Female	9 22.5%	2 33.3%	11 23.9%
Male	31 77.5%	4 66.7%	35 76.1%
Race/Ethnicity, Customized (participants) [Number]
Hispanic / Latino	0 0%	6 100%	6 13%
Not Hispanic / Latino	18 45%	0 0%	18 39.1%
Missing	22 55%	0 0%	22 47.8%
Race/Ethnicity, Customized (participants) [Number]
Black/ African American	40 100%	0 0%	40 87%
White	0 0%	6 100%	6 13%
Region of Enrollment (participants) [Number]
Brazil	21 52.5%	0 0%	21 45.7%
Mexico	0 0%	2 33.3%	2 4.3%
South Africa	3 7.5%	0 0%	3 6.5%
United States	16 40%	4 66.7%	20 43.5%
Hepatitis B surface antigen (HBsAg) status at baseline (participants) [Number]
Positive	40 100%	4 66.7%	44 95.7%
Negative	0 0%	0 0%	0 0%
Missing	0 0%	2 33.3%	2 4.3%
Hepatitis B e antigen (HBeAg) status at baseline (participants) [Number]
Positive	22 55%	4 66.7%	26 56.5%
Negative	18 45%	2 33.3%	20 43.5%
Hepatitis B e antibody (HBeAb) at baseline (participants) [Number]
Positive	19 47.5%	2 33.3%	21 45.7%
Negative	21 52.5%	4 66.7%	25 54.3%
Alanine Aminotransferase (ALT) (U/L) [Median (Full Range) ]
Median (Full Range) [U/L]	106	113	107
Albumin (g/dL) [Median (Full Range) ]
Median (Full Range) [g/dL]	4.3	4.3	4.3
Total Bilirubin (mg/dL) [Median (Full Range) ]
Median (Full Range) [mg/dL]	0.6	0.5	0.6

Outcome Measures

1. Secondary Outcome

Title	Percentage of Participants Who Achieve HBV DNA < Lower Limit of Quantitation (LOQ = 29 IU/mL [Approximately 169 Copies/mL]) at Week 48
Description	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep 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.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number (95% Confidence Interval) [percentage of participants]	12.5 31.3%	13.0 216.7%

2. Secondary Outcome

Title	Percentage of Participants With HBV DNA by PCR Category at Week 48
Description	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
<50 IU/mL (< 300 copies/mL)	72.5 181.3%	69.6 1160%
50 to <172 IU/mL (300 to < 103 copies/mL)	0 0%	0 0%
172 to <1720 IU/mL (103 to < 104 copies/mL)	10.0 25%	10.9 181.7%
1720 to <17200 IU/mL (104 to < 105 copies/mL)	5.0 12.5%	4.3 71.7%
≥17,200 IU/mL (≥105 copies/mL)	0 0%	0 0%
Missing	12.5 31.3%	15.2 253.3%

3. Secondary Outcome

Title	Percentage of Participants With Virologic Rebound Through Week 48 While on Continued Dosing With ETV
Description	Virologic rebound is defined as a confirmed increase of ≥ 1 log10 in HBV DNA from the participant's nadir value (2 sequential HBV DNA measurements or last on-treatment measurement)
Time Frame	through Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. The participants who discontinued prior to Week 48 were counted as failure.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number [percentage of participants]	0 0%	0 0%

4. Secondary Outcome

Title	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
Description	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.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number [percentage of participants]	67.5 168.8%	67.4 1123.3%

5. Secondary Outcome

Title	Percentage of Participants With Confirmed HBeAg Loss at Week 48 (for HBeAg-positive Participants Only)
Description	HBeAg is a hepatitis B viral protein. HBeAg loss = HBeAg-negative at the specified analysis week
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Treated HBeAg-positive participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	22	26
Number [percentage of participants]	50.0 125%	53.8 896.7%

6. Secondary Outcome

Title	Percentage of Participants With HBeAg Seroconversion at Week 48 (for HBeAg-positive Participants Only)
Description	HBeAg is a hepatitis B viral protein. HBeAg Seroconversion = HBeAg Loss and Presence of Hepatitis B e Antibody (HBeAb).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Treated HBeAg-positive participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	22	26
Number [percentage of participants]	40.9 102.3%	46.2 770%

7. Secondary Outcome

Title	Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Description	HBsAg = a part of the hepatitis B virus that, when in the blood, is a marker of infection. HBsAg loss = HBsAg-negative at the specified analysis week.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number [percentage of participants]	5.0 12.5%	6.5 108.3%

8. Secondary Outcome

Title	Percentage of Participants With HBsAg Seroconversion at Week 48
Description	HBsAg = a part of the hepatitis B virus that, when in the blood, is a of infection. HBs seroconversion is defined as HBsAg loss with positive HBsAb.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant was missing the efficacy assessments for a visit, this is considered a failure and was counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number [percentage of participants]	2.5 6.3%	4.3 71.7%

9. Secondary Outcome

Title	Mean log10 Reduction From Baseline in HBV DNA at Week 48
Description	HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan TaqMan AmpliPrep assay. Reduction in log10 HBV count=reduced viral load.
Time Frame	baseline, Week 48

Outcome Measure Data

Analysis Population Description

All treated participants. The participants who discontinued prior to Week 48 were counted as failure.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	35	39
Baseline	7.1 (0.26)	7.0 (0.25)
HBV DNA at Week 48	1.88 (0.100)	1.87 (0.091)
Change from baseline	-5.22 (0.249)	-5.18 (0.231)

10. Secondary Outcome

Title	Percentage of Participants With HBV DNA < Other IU Cut-off Points That May be Clinically Relevant at the Time of Data Analysis
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Since there were no other cut-off points other than those at the time of data analysis, this outcome was not analysed.

Arm/Group Title	Black / African American	Total
Arm/Group Description	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks
Measure Participants	0	0

11. Secondary Outcome

Title	Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to Adverse Events
Description	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.
Time Frame	From enrollment through Week 52 + 5 days

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Black / African American	Hispanic	Total
Arm/Group Description	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks
Measure Participants	40	6	46
Deaths	0 0%	0 0%	0 0%
SAEs	3 7.5%	1 16.7%	4 8.7%
Discontinuations Due to AEs	0 0%	0 0%	0 0%
Any AE	33 82.5%	5 83.3%	38 82.6%
Grade 3 - 4 AEs	5 12.5%	1 16.7%	6 13%
Related AEs	16 40%	0 0%	16 34.8%
Grade 2 - 4 Related AEs	5 12.5%	0 0%	5 10.9%

12. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF): Hematology
Description	Criteria for hematology abnormalities were graded using the modified WHO grading system. 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.
Time Frame	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Black / African American	Total
Arm/Group Description	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Hemoglobin-OT	1 2.5%	2 33.3%
Hemoglobin-OF; n=26 , 29	0 0%	0 0%
White Blood Cells-OT	15 37.5%	18 300%
White Blood Cells-OF; n=26 , 29	7 17.5%	8 133.3%
Neutrophils -OT	13 32.5%	13 216.7%
Neutrophils-OF; n=26 , 26	4 10%	4 66.7%
Platelets-OT	4 10%	4 66.7%
Platelets-OF; n=26 , 29	0 0%	0 0%
International Normalized Ratio-OT	18 45%	23 383.3%
International Normalized Ratio-OF; n=26 , 29	4 10%	4 66.7%

13. Primary Outcome

Title	Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) < 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 48
Description	HBV DNA assessments were performed using the Roche COBAS® TaqMan AmpliPrep assay. HBV DNA < 50 IU/mL = approximately <300 copies/mL.
Time Frame	Week 48 of ETV treatment

Outcome Measure Data

Analysis Population Description

All treated participants. If a participant is missing the efficacy assessments for a visit, this is considered a failure and is counted as evaluable.

Arm/Group Title	Black / African American	Total
Arm/Group Description	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks	ETV tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Number (95% Confidence Interval) [percentage of participants]	72.5 181.3%	69.6 1160%

14. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) : Serum Chemistry
Description	The modified World Health Oranization(WHO)grading system was used to grade the abnormalities. ULN=upper limit of normal. Alanine aminotransferase:>1.25xULN, Aspartate aminotransferase:>1.25xULN, Alkaline Phosphatase:>1.25xULN, Total Bilirubin:>1.1xULN, Serum Lipase:>1.10xULN, Creatinine:>1.1xULN, Blood Urea Nitrogen:1.25xULN, 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
Time Frame	OT: From start of study therapy through Week 52 + 5 days; OF= End of OT period + 24-week follow-up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Black / African American	Total
Arm/Group Description	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks	Entecavir tablets, Oral, 0.5 mg, once daily, up to 52 weeks (Includes 6 participants of the Hispanic cohort)
Measure Participants	40	46
Alanine aminotransferase-OT	37 92.5%	43 716.7%
Alanine aminotransferase-OF; n=26 , 29	3 7.5%	4 66.7%
Aspartate aminotransferase-OT	33 82.5%	38 633.3%
Aspartate aminotransferase-OF; n=26 , 29	2 5%	3 50%
Alkaline Phosphatase-OT	3 7.5%	3 50%
Alkaline Phosphatase-OF; n=26 , 29	1 2.5%	1 16.7%
Albumin-OT	3 7.5%	5 83.3%
Albumin-OF; n=26 , 29	0 0%	0 0%
Total Bilirubin-OT	7 17.5%	7 116.7%
Total Bilirubin-OF; n=26 , 29	3 7.5%	4 66.7%
Serum Lipase-OT	12 30%	14 233.3%
Serum Lipase-OF; n=26 , 29	1 2.5%	1 16.7%
Creatinine-OT	3 7.5%	3 50%
Creatinine-OF; n=26 , 29	0 0%	0 0%
Blood Urea Nitrogen-OT	2 5%	2 33.3%
Blood Urea Nitrogen-OF; n=26 , 29	0 0%	0 0%
Hyperglycemia-OT	14 35%	15 250%
Hyperglycemia-OF; n=26 , 29	5 12.5%	5 83.3%
Hypoglycemia-OT	5 12.5%	5 83.3%
Hypoglycemia-OF; n=26 , 29	1 2.5%	1 16.7%
Hypernatremia-OT	0 0%	0 0%
Hypernatremia-OF; n=26 , 29	0 0%	0 0%
Hyponatremia-OT	3 7.5%	3 50%
Hyponatremia-OF; n=26 , 29	0 0%	1 16.7%
Hyperkalemia-OT	0 0%	0 0%
Hyperkalemia-OF; n=26 , 29	0 0%	0 0%
Hypokalemia-OT	3 7.5%	3 50%
Hypokalemia-OF; n=26 , 29	0 0%	0 0%
Hyperchloremia-OT	0 0%	0 0%
Hyperchloremia-OF; n=26 , 29	0 0%	0 0%
Hypochloremia-OT	0 0%	0 0%
Hypochloremia-OF; n=26 , 29	0 0%	0 0%

Adverse Events

Time Frame	52 Weeks
Arm/Group Title	Entecavir (ETV)
Arm/Group Description	Entecavir tablets, Oral, 0.5 mg, once daily, up to 48 weeks (Includes 6 participants of the Hispanic cohort)
All Cause Mortality
	Entecavir (ETV)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Entecavir (ETV)
	Affected / at Risk (%)	# Events
Total	4/46 (8.7%)
Blood and lymphatic system disorders
LEUKOCYTOSIS	1/46 (2.2%)
Cardiac disorders
ANGINA PECTORIS	1/46 (2.2%)
Gastrointestinal disorders
ASCITES	1/46 (2.2%)
General disorders
PYREXIA	1/46 (2.2%)
Infections and infestations
LOBAR PNEUMONIA	1/46 (2.2%)
PNEUMONIA	1/46 (2.2%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/46 (2.2%)
BLOOD GLUCOSE ABNORMAL	1/46 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CELL CARCINOMA	1/46 (2.2%)
Nervous system disorders
HEADACHE	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	Entecavir (ETV)
	Affected / at Risk (%)	# Events
Total	21/46 (45.7%)
Gastrointestinal disorders
ABDOMINAL PAIN	6/46 (13%)
DIARRHOEA	5/46 (10.9%)
NAUSEA	4/46 (8.7%)
General disorders
PYREXIA	4/46 (8.7%)
FATIGUE	4/46 (8.7%)
Infections and infestations
URINARY TRACT INFECTION	3/46 (6.5%)
NASOPHARYNGITIS	3/46 (6.5%)
INFLUENZA	4/46 (8.7%)
Musculoskeletal and connective tissue disorders
BACK PAIN	4/46 (8.7%)
MYALGIA	3/46 (6.5%)
Nervous system disorders
SOMNOLENCE	3/46 (6.5%)
HEADACHE	8/46 (17.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication