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

• ClinicalTrials.gov Identifier: NCT00076336
• Recruitment Status: Completed
• First Posted: January 22, 2004
• Results First Posted: September 5, 2011
• Last Update Posted: September 5, 2011
• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis; Hepatitis B, Chronic; Cirrhosis	Drug: Telbivudine; Drug: Lamivudine; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind Trial of Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis
• Study Start Date: December 2003
• Actual Primary Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Telbivudine 600 mg; 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.	Drug: Telbivudine; 600mg/day oral tablet for 104 weeks; Other Name: LDT600; Drug: Placebo; Telbivudine matching placebo or lamivudine matching placebo tablet.
Active Comparator: Lamivudine 100 mg; 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.	Drug: Lamivudine; 100mg/day oral tablet for 104 weeks; Drug: Placebo; Telbivudine matching placebo or lamivudine matching placebo tablet.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Clinical Response [ Time Frame: From Baseline to Week 52 ]
   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 :

1. Time to Initial Clinical Response [ Time Frame: From Baseline to Week 104 ]
   Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.
2. Duration of Initial Clinical Response [ Time Frame: Baseline to Week 104 ]
   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.
3. Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 [ Time Frame: From Baseline to weeks 52 and 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.
4. Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score [ Time Frame: Baseline and Week 104 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Phoenix, Arizona, United States

United States, California

Los Angeles, California, United States

United States, Colorado

Denver, Colorado, United States

United States, Indiana

Indianapolis, Indiana, United States

United States, Minnesota

Rochester, Minnesota, United States

United States, New York

New York, New York, United States

United States, Texas

Houston, Texas, United States

United States, Wisconsin

Madison, Wisconsin, United States

Australia

Heidelburg, Australia

Canada

Winnipeg, Canada

China

Hong Kong, China

France

Villejuif Cedex, France

Germany

Hannover, Germany

India

Novartis

New Delhi, India

Israel

Tel Aviv, Israel

Korea, Republic of

Seoul, Korea, Republic of

Latvia

Novartis

Riga, Latvia

Malaysia

Novartis

Kuala Lumpur, Malaysia

New Zealand

Auckland, New Zealand

Poland

Novartis

Krakow, Poland

Russian Federation

Novartis

Moscow, Russian Federation

Singapore

Singapore, Singapore

Spain

Barcelona, Spain

Taiwan

Taipei, Taiwan

Thailand

Bangkok, Thailand

Turkey

Novartis

Istanbul, Turkey

United Kingdom

London, United Kingdom

Vietnam

Novartis

Hanoi, Vietnam

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

Publications of Results:

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

• Responsible Party: External Affairs, Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00076336
• Other Study ID Numbers: CLDT600A2301
• First Posted: January 22, 2004
• Results First Posted: September 5, 2011
• Last Update Posted: September 5, 2011
• Last Verified: August 2011

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Liver Cirrhosis; Fibrosis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Pathologic Processes; Lamivudine; Telbivudine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents