Antiviral Activity of Entecavir in Patients Receiving Liver Transplant Due to Chronic Hepatitis B Virus Infection

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00395018

First received: November 1, 2006

Last updated: April 30, 2012

Last verified: April 2012

History of Changes

Results First Received: March 29, 2012

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Prevention
Condition:	Hepatitis B, Chronic
Intervention:	Drug: entecavir

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 109 participants were enrolled at 27 investigative sites.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 109 participants enrolled, 65 were treated and 61 received therapy for at least 1 month. Of the 44 participants who were never treated, 23 no longer met study criteria, 9 due to administrative reason by sponsor, 6 withdrew consent, 3 due to other reasons, 2 died, 1 due to poor/non-compliance.

Reporting Groups

	Description
Entecavir (ETV)	ETV tablets, Oral, 1.0 mg, once daily, up to 72 weeks

Participant Flow for 2 periods

Period 1: On-Treatment

	Entecavir (ETV)
STARTED	65 ^[1]
DISCONTINUED PRIOR TO WEEK 72 VISIT	10
DISCONTINUED AT OR AFTER WEEK 72 VISIT	0
COMPLETED	55 ^[2]
NOT COMPLETED	10
Death	4
Other Reason	2
Poor/non-compliance	2
Subject no longer meets study criteria	2

[1]	Started = treated (participants who received at least 1 dose of study therapy)
[2]	"Completed" means received treatment through Week 72

Period 2: Off-Treatment Follow-up

	Entecavir (ETV)
STARTED	5 ^[1]
COMPLETED	1 ^[2]
NOT COMPLETED	4
Followup no longer required per protocol	1
Lost to Follow-up	2
Poor/non-compliance	1

[1]	Treated participants who discontinued =<72 weeks and did not start other anti-HBV therapy
[2]	"Completed" means completed the study

Baseline Characteristics

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Reporting Groups

	Description
Entecavir (ETV)	ETV tablets, Oral, 1.0 mg, once daily, up to 72 weeks

Baseline Measures

	Entecavir (ETV)
Number of Participants [units: participants]	65
Age [units: years] Median ( Full Range )	51.0 ( 23 to 68 )
Age, Customized [units: participants]
21-64 years	60
>=65 years	5
Gender [units: participants]
Female	12
Male	53
Race/Ethnicity, Customized [units: participants]
Asian	24
Black/African American	7
Native Hawaiian/Other Pacific Islander	1
White	25
Other	8
Race/Ethnicity, Customized ^[1] [units: participants]
Hispanic/Latino	0
Not Hispanic/Latino	14
Region of Enrollment [units: participants]
Argentina	2
Australia	5
Brazil	12
France	12
Italy	6
Korea, Republic of	7
Spain	3
Taiwan	4
United States	14
HBV DNA by PCR [units: log10 IU/mL] Median ( Full Range )	0.8 ( 0.8 to 3.7 )
Hepatitis B Surface Antigen [units: participants]
Positive	61
Negative	4
Hepatitis B E Antigen (HBeAg) [units: participants]
Positive	7
Negative	58
Hepatitis B E Antibody (HBeAb) [units: participants]
Positive	48
Negative	17
International Normalized Ratio ^[2] [units: ratio] Median ( Full Range )	1.51 ( 0.86 to 7.10 )
Albumin [units: g/dL] Median ( Full Range )	3.0 ( 1.8 to 4.7 )
Alanine Aminotransferase (ALT) [units: U/L] Median ( Full Range )	43 ( 10 to 1485 )
Total Bilirubin [units: mg/dL] Median ( Full Range )	2.4 ( 0.2 to 31.0 )

[1]	Participants in United States of America (USA) only.
[2]	Evaluated in 63 participants at baseline.

Outcome Measures

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1. Primary:

Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) => 50 IU/mL by Polymerase Chain Reaction (PCR) at Week 72 [ Time Frame: At 72 weeks ]

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2. Primary:

Number of Participants With HBV DNA by PCR >= 50 IU/mL Through Week 72 [ Time Frame: At baseline (day 1), week 12, 24, 36, 48, 60, and 72 ]

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3. Secondary:

Distribution of ALT Levels Through 72 Weeks: Overall [ Time Frame: On Day 1 (baseline) and at week 4, 12, 24, 36, 48, 60, 72 ]

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4. Secondary:

Percentage of Participants With HBV DNA < 50 IU/mL (Approximately 300 Copies/mL) by PCR at the End of Post-dosing Follow-up [ Time Frame: At 72 weeks + 24 weeks follow-up ]

Show Outcome Measure 4

5. Secondary:

Percentage of Participants With HBeAg Loss at Week 72 (for HBeAg-positive Participants) [ Time Frame: At week 72 ]

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6. Secondary:

Percentage of Participants With HBeAg Seroconversion at Week 72 (for HBeAg-positive Participants) [ Time Frame: At week 72 ]

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7. Secondary:

Percentage of Participants With HBsAg Loss at Week 72 [ Time Frame: At week 72 ]

Show Outcome Measure 7

8. Secondary:

Percentage of Participants With HBsAg Seroconversion at Week 72 [ Time Frame: At week 72 ]

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9. Secondary:

Percentage of Participants With HBsAg Recurrence At Week 72 [ Time Frame: At week 72 ]

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10. Secondary:

Total Bilirubin at Week 72 [ Time Frame: At week 72 ]

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11. Secondary:

Prothrombin Time (PT) at Week 72 [ Time Frame: At week 72 ]

Show Outcome Measure 11

12. Secondary:

Number of Participants With Liver Rejection Through Week 72 [ Time Frame: Through week 72 ]

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13. Secondary:

Number of Participants With Re-transplantation Through Week 72 [ Time Frame: Through week 72 ]

Show Outcome Measure 13

14. Secondary:

Participants With Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations From Study Drug Due to AEs (On-treatment [OT] and Off-treatment Follow-up [OF]) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ]

Show Outcome Measure 14

15. Secondary:

Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment Follow-up(OF): Hematology (All Grades) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ]

Show Outcome Measure 15

16. Secondary:

Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) [ Time Frame: OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up ]

Hide Outcome Measure 16

Measure Type	Secondary
Measure Title	Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades)
Measure Description	Normal ranges are local lab data and vary according to the site. Criteria for laboratory abnormalities:ALT:>1.25xULN;AST:>1.25xULN;ALP:>1.25xULN;Total Bilirubin:>1.1xULN;Serum Lipase:>1.10xULN;Creatinine:>1.1xULN;Blood Urea Nitrogen:>1.25xULN;Hyperglycemia:>116mg/dL;Hypoglycemia:<64mg/dL;Hyponatremia:<132meq/L;Hypernatremia:>148meq/L;Hypokalemia:<3.4meq/L;hyperkalemia:>5.6meq/L;Hypochloremia:<93meq/L;Hyperchloremia:>113meq/L;Albumin: Decrease >= 1g/dL from baseline and < 3 g/dL. HYPER=value>ULN(upper limit of normal). HYPO=value<LLN (lower limit of normal).
Time Frame	OT:From start of dosing through Week 72 + 5 days; OF:End of OT through 24-weeks follow-up
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated population: Participants who received atleast 1 dose of study drug.

Reporting Groups

	Description
Entecavir (ETV)	ETV tablets, Oral, 1.0 mg, once daily, up to 72 weeks

Measured Values

	Entecavir (ETV)
Number of Participants Analyzed [units: participants]	65
Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades) [units: participants]
ALANINE AMINOTRANSFERASE (ALT)-OT	54
ALT-OF (n=4)	0
ASPARTATE AMINOTRANSFERASE (AST)-OT	56
AST-OF (n=4)	0
ALKALINE PHOSPHATASE (ALP)-OT	34
ALP-OF (n=4)	1
ALBUMIN-OT (n=64)	51
ALBUMIN-OF (n=3)	0
TOTAL BILIRUBIN-OT	57
TOTAL BILIRUBIN-OF (n=4)	0
SERUM LIPASE-OT (n=64)	37
SERUM LIPASE-OF (n=3)	1
CREATININE-OT	43
CREATININE-OF (n=4)	0
BLOOD UREA NITROGEN-OT	43
BLOOD UREA NITROGEN-OF (n=4)	0
HYPERGLYCEMIA-OT (n=64)	52
HYPERGLYCEMIA-OF (n=3)	0
HYPOGLYCEMIA-OT (n=64)	15
HYPOGLYCEMIA-OF (n=3)	0
HYPERNATREMIA-OT	7
HYPERNATREMIA-OF (n=4)	0
HYPONATREMIA-OT	14
HYPONATREMIA-OF (n=4)	0
HYPERKALEMIA-OT	15
HYPERKALEMIA-OF (n=4)	0
HYPOKALEMIA-OT	22
HYPOKALEMIA-OF (n=4)	0
HYPERCHLOREMIA-OT	11
HYPERCHLOREMIA-OF (n=4)	0
HYPOCHLOREMIA-OT	7
HYPOCHLOREMIA-OF (n=4)	0

No statistical analysis provided for Number of Participants With Laboratory Abnormalities On-treatment (OT) and Off-Treatment (OF) Follow-up: Serum Chemistry (All Grades)

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00395018 History of Changes
Other Study ID Numbers:	AI463-109
Study First Received:	November 1, 2006
Results First Received:	March 29, 2012
Last Updated:	April 30, 2012
Health Authority:	United States: Food and Drug Administration

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