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Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

Primary Purpose

Hepatitis, Hepatitis B, Chronic, Cirrhosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Telbivudine
Lamivudine
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Documented decompensated chronic hepatitis B defined by all of the following: 1. Clinical history compatible with decompensated chronic hepatitis B related cirrhosis; 2. Child-Turcotte-Pugh score > 7 points. Evidence of hepatic cirrhosis or portal hypertension. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Patient is pregnant or breastfeeding. Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV). Patient previously received lamivudine, adefovir, or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog at any time Patient has received interferon or other immunomodulatory treatment for HBV infection in the 12 months before Screening for this study. Other protocol-defined exclusion criteria may apply.

Sites / Locations

  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis
  • Novartis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Telbivudine 600 mg

Lamivudine 100 mg

Arm Description

Participants received Telbivudine 600 mg and a matching lamivudine placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.

Lamivudine 100 mg and a Telbivudine matching placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.

Outcomes

Primary Outcome Measures

Number of Participants With Clinical Response
Clinical response defined as achieving all of the following 3 criteria on at least 2 consecutive visits or at the last on-treatment visit: Serum hepatitis B virus (HBV) DNA < 4 log10 copies/mL, normal Alanine transaminase (ALT) level (ALT ≤ Upper Limit of Normal (ULN)), and improvement (a 2- point or greater reduction in Child-Turcotte-Pugh (CTP) score) or stabilization (not more than a 1-point change in CTP score), compared to the baseline value. CTP scores range from 5-15, higher scores indicate more liver impairment. For Improvement/Stabilization, either of the individual criteria were met.

Secondary Outcome Measures

Time to Initial Clinical Response
Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.
Duration of Initial Clinical Response
Kaplan-Meier method was used. The duration was calculated as: date of last visit before initial loss of clinical response - date of initial clinical response occurred+1. If a patient did not lose clinical response, it was then censored at the efficacy overall censoring date.
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104
Child-Turcotte-Pugh (CTP) uses 2 clinical variables, ascites and encephalopathy, and 3 laboratory parameters, serum bilirubin, albumin, and prothrombin time. Each variable is assigned a score from 1 to 3, with the combined score comprising the CTP score range of 5 to 15 points. Higher scores indicate more impaired liver function. "Worsening" of CTP score was defined as a 2-point or greater increase from baseline, "improvement" in CTP score was defined as a 2-point or greater reduction from baseline, and "stabilization" of CTP score was defined as a change of 1-point or less from baseline.
Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score
Modified CTP was calculated using the 3 biochemical-components (serum bilirubin, albumin, and prothrombin). Total scores range from 3-9; higher scores indicate more liver impairment. Improvement was defined as 2-point or greater reduction in score from baseline. Stabilization comprises a score change of 1-point or less from baseline. Worsening of CTP score was defined as a 2-point or greater increase from baseline. The rationale for assessing changes in this modified (3-component) CTP score is that this maneuver removed the two subjective components of CTP scoring (ascites and encephalopathy).

Full Information

First Posted
January 20, 2004
Last Updated
August 4, 2011
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00076336
Brief Title
Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis
Official Title
Randomized, Double-Blind Trial of Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
December 2003 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
This research study was conducted to compare the safety and effectiveness of the investigational medication, LdT (Telbivudine) versus Lamivudine, a drug currently approved by the US, European and Asian Health Authorities for the treatment of Hepatitis B infection. The results for patients taking LdT will be compared to results for patients taking lamivudine.
Detailed Description
Multicenter, multinational, randomized, double-blind study designed to compare the safety and efficacy of telbivudine (600 mg/day) versus lamivudine (100 mg/day) for 104 weeks in adults with decompensated chronic hepatitis B and evidence of cirrhosis. Patients were pre-stratified by screening Child-Turcotte-Pugh score (CTP score < 9 or ≥ 9) and ALT level (within normal limits (WNL) or > 1.0 x ULN) to help assure similar degrees of hepatic insufficiency and liver inflammation on both treatment arms. After 104 weeks of treatment, participants were followed-up with for an additional 16 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis, Hepatitis B, Chronic, Cirrhosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
232 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Telbivudine 600 mg
Arm Type
Experimental
Arm Description
Participants received Telbivudine 600 mg and a matching lamivudine placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.
Arm Title
Lamivudine 100 mg
Arm Type
Active Comparator
Arm Description
Lamivudine 100 mg and a Telbivudine matching placebo orally once a day for up to 104 weeks. Participants were followed-up for 16 weeks post-treatment.
Intervention Type
Drug
Intervention Name(s)
Telbivudine
Other Intervention Name(s)
LDT600
Intervention Description
600mg/day oral tablet for 104 weeks
Intervention Type
Drug
Intervention Name(s)
Lamivudine
Intervention Description
100mg/day oral tablet for 104 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Telbivudine matching placebo or lamivudine matching placebo tablet.
Primary Outcome Measure Information:
Title
Number of Participants With Clinical Response
Description
Clinical response defined as achieving all of the following 3 criteria on at least 2 consecutive visits or at the last on-treatment visit: Serum hepatitis B virus (HBV) DNA < 4 log10 copies/mL, normal Alanine transaminase (ALT) level (ALT ≤ Upper Limit of Normal (ULN)), and improvement (a 2- point or greater reduction in Child-Turcotte-Pugh (CTP) score) or stabilization (not more than a 1-point change in CTP score), compared to the baseline value. CTP scores range from 5-15, higher scores indicate more liver impairment. For Improvement/Stabilization, either of the individual criteria were met.
Time Frame
From Baseline to Week 52
Secondary Outcome Measure Information:
Title
Time to Initial Clinical Response
Description
Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.
Time Frame
From Baseline to Week 104
Title
Duration of Initial Clinical Response
Description
Kaplan-Meier method was used. The duration was calculated as: date of last visit before initial loss of clinical response - date of initial clinical response occurred+1. If a patient did not lose clinical response, it was then censored at the efficacy overall censoring date.
Time Frame
Baseline to Week 104
Title
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104
Description
Child-Turcotte-Pugh (CTP) uses 2 clinical variables, ascites and encephalopathy, and 3 laboratory parameters, serum bilirubin, albumin, and prothrombin time. Each variable is assigned a score from 1 to 3, with the combined score comprising the CTP score range of 5 to 15 points. Higher scores indicate more impaired liver function. "Worsening" of CTP score was defined as a 2-point or greater increase from baseline, "improvement" in CTP score was defined as a 2-point or greater reduction from baseline, and "stabilization" of CTP score was defined as a change of 1-point or less from baseline.
Time Frame
From Baseline to weeks 52 and 104
Title
Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score
Description
Modified CTP was calculated using the 3 biochemical-components (serum bilirubin, albumin, and prothrombin). Total scores range from 3-9; higher scores indicate more liver impairment. Improvement was defined as 2-point or greater reduction in score from baseline. Stabilization comprises a score change of 1-point or less from baseline. Worsening of CTP score was defined as a 2-point or greater increase from baseline. The rationale for assessing changes in this modified (3-component) CTP score is that this maneuver removed the two subjective components of CTP scoring (ascites and encephalopathy).
Time Frame
Baseline and Week 104

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented decompensated chronic hepatitis B defined by all of the following: 1. Clinical history compatible with decompensated chronic hepatitis B related cirrhosis; 2. Child-Turcotte-Pugh score > 7 points. Evidence of hepatic cirrhosis or portal hypertension. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Patient is pregnant or breastfeeding. Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV). Patient previously received lamivudine, adefovir, or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog at any time Patient has received interferon or other immunomodulatory treatment for HBV infection in the 12 months before Screening for this study. Other protocol-defined exclusion criteria may apply.
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
New York
State/Province
New York
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Madison
State/Province
Wisconsin
Country
United States
City
Heidelburg
Country
Australia
City
Winnipeg
Country
Canada
City
Hong Kong
Country
China
City
Villejuif Cedex
Country
France
City
Hannover
Country
Germany
Facility Name
Novartis
City
New Delhi
Country
India
City
Tel Aviv
Country
Israel
City
Seoul
Country
Korea, Republic of
Facility Name
Novartis
City
Riga
Country
Latvia
Facility Name
Novartis
City
Kuala Lumpur
Country
Malaysia
City
Auckland
Country
New Zealand
Facility Name
Novartis
City
Krakow
Country
Poland
Facility Name
Novartis
City
Moscow
Country
Russian Federation
City
Singapore
Country
Singapore
City
Barcelona
Country
Spain
City
Taipei
Country
Taiwan
City
Bangkok
Country
Thailand
Facility Name
Novartis
City
Istanbul
Country
Turkey
City
London
Country
United Kingdom
Facility Name
Novartis
City
Hanoi
Country
Vietnam

12. IPD Sharing Statement

Citations:
Citation
E.J. Gane, H.L. Chan, G. Choudhuri, D.J. Suh4, A. Chutaputti, R. Safadi, T. Tanwandee, S. Thongsawat, N. Assy, S.K. Sarin, W. Bao, A. Trylesinski, C. Avila. TREATMENT OF DECOMPENSATED HBV-CIRRHOSIS: RESULTS FROM 2-YEARS RANDOMIZED TRIAL WITH TELBIVUDINE OR LAMIVUDINE. Journal of Hepatology 52, Supplement 1, Page S4. April 2010
Results Reference
result

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Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis

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