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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00076336
• Collaborator: (none)
• Enrollment: 232
• Locations: 28
• Arms: 2
• Patients Per Site: 8.3

Study Details

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
• 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: Dec 1, 2003
• Actual Primary Completion Date: Dec 1, 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 Names: 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 [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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 16 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented decompensated chronic hepatitis B defined by all of the following: 1. Clinical history compatible with decompensated chronic hepatitis B related cirrhosis;

1. 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

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States
2		Los Angeles	California	United States
3		Denver	Colorado	United States
4		Indianapolis	Indiana	United States
5		Rochester	Minnesota	United States
6		New York	New York	United States
7		Houston	Texas	United States
8		Madison	Wisconsin	United States
9		Heidelburg		Australia
10		Winnipeg		Canada
11		Hong Kong		China
12		Villejuif Cedex		France
13		Hannover		Germany
14	Novartis	New Delhi		India
15		Tel Aviv		Israel
16		Seoul		Korea, Republic of
17	Novartis	Riga		Latvia
18	Novartis	Kuala Lumpur		Malaysia
19		Auckland		New Zealand
20	Novartis	Krakow		Poland
21	Novartis	Moscow		Russian Federation
22		Singapore		Singapore
23		Barcelona		Spain
24		Taipei		Taiwan
25		Bangkok		Thailand
26	Novartis	Istanbul		Turkey
27		London		United Kingdom
28	Novartis	Hanoi		Vietnam

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00076336
• Other Study ID Numbers: CLDT600A2301
• First Posted: Jan 22, 2004
• Last Update Posted: Sep 5, 2011
• Last Verified: Aug 1, 2011

• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Liver Cirrhosis; Fibrosis; Lamivudine; Telbivudine

Study Results

Participant Flow

Pre-assignment Detail	232 patients randomized. One randomized patient in the telbivudine treatment group discontinued prior to commencing treatment and was excluded from the intent to treat (ITT) population. Three randomized patients (two in lamivudine group and one in telbivudine group) had no HBV DNA assessments after baseline and were excluded from ITT population.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Period Title: Overall Study
STARTED	116	116
Safety Population	115	116
Intent to Treat (ITT) Population	114	114
Completed Week 52	97	94
Completed Week 104	70	62
COMPLETED	64	60
NOT COMPLETED	52	56

Baseline Characteristics

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg	Total
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Total of all reporting groups
Overall Participants	114	114	228
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.6 (10.88)	51.9 (9.98)	50.8 (10.48)
Age, Customized (Number) [Number]
< 30 years	6 5.3%	2 1.8%	8 3.5%
Between 30 and 50 years	44 38.6%	44 38.6%	88 38.6%
> 50 years	64 56.1%	68 59.6%	132 57.9%
Sex: Female, Male (Count of Participants)
Female	27 23.7%	33 28.9%	60 26.3%
Male	87 76.3%	81 71.1%	168 73.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was on the intention-to-treat (ITT) population.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Measure Participants	114	114
Clinical Response	65 57%	62 54.4%
HBV DNA < 4log10copies/mL	85 74.6%	82 71.9%
Normal ALT	78 68.4%	81 71.1%
Improvement/stabilization in CTP	96 84.2%	96 84.2%
Improvement in CTP (reduction ≥ 2)	34 29.8%	43 37.7%
Stabilization in CTP (absolute change ≤ 1)	56 49.1%	48 42.1%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was on intention-to-treat (ITT) population. Only the observed time to initial clinical response was summarized.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Measure Participants	95	92
Mean (Standard Deviation) [Days]	137.5 (126.14)	125.2 (111.24)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was on intention-to-treat (ITT) population. Only patients who achieved clinical response were considered.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Measure Participants	95	92
Mean (Standard Error) [Days]	473.1 (26.13)	456.3 (24.97)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was done per intention-to-treat (ITT) population. Last Observation Carried Forward (LOCF) was utilized for missing data, with the exception of missing observations due to treatment failure, death or AE, which were imputed as "worsening" CTP.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Measure Participants	114	114
Improvement At Week 52	36 31.6%	44 38.6%
Stabilization At Week 52	60 52.6%	52 45.6%
Worsening At Week 52	18 15.8%	18 15.8%
Improvement At Week 104	44 38.6%	46 40.4%
Stabilization At Week 104	42 36.8%	38 33.3%
Worsening At Week 104	28 24.6%	30 26.3%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis was done on the intention-to-treat (ITT) population. Last Observation Carried Forward (LOCF) was utilized for missing data, with the exception of missing observations due to treatment failure, death or AE, which were imputed as "worsening" CTP.

Arm/Group Title	Telbivudine 600 mg	Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.	Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
Measure Participants	114	114
Improvement at Week 104	30 26.3%	31 27.2%
Stabilization at Week 104	57 50%	54 47.4%
Worsening at Week 104	27 23.7%	29 25.4%

Adverse Events

Adverse Event Reporting Description	Adverse event data is provided for the "on- treatment" period - i.e. any AEs started in the period of first dose date to last dose date + 30 days (all inclusive). For follow-up period, no individual preferred terms were reported in any treatment group. Hence, AE for follow-up period is not included here.
Arm/Group Title	Telbivudine 600 mg		Lamivudine 100 mg
Arm/Group Description	Participants received Telbivudine 600 mg and a matching placebo to lamivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.		Participants received Lamivudine 100 mg and matching placebo to Telbivudine orally once a day for up to 104 weeks, followed by a 16-week follow-up period.
All Cause Mortality
	Telbivudine 600 mg		Lamivudine 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Telbivudine 600 mg		Lamivudine 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/115 (51.3%)		68/116 (58.6%)
Blood and lymphatic system disorders
Anaemia	0/115 (0%)		1/116 (0.9%)
Cardiac disorders
Sinus bradycardia	1/115 (0.9%)		0/116 (0%)
Gastrointestinal disorders
Abdominal pain	2/115 (1.7%)		0/116 (0%)
Abdominal pain upper	1/115 (0.9%)		0/116 (0%)
Abdominal strangulated hernia	0/115 (0%)		1/116 (0.9%)
Ascites	11/115 (9.6%)		2/116 (1.7%)
Duodenal ulcer	0/115 (0%)		1/116 (0.9%)
Duodenal ulcer haemorrage	0/115 (0%)		1/116 (0.9%)
Enteritis	0/115 (0%)		1/116 (0.9%)
Food poisoning	0/115 (0%)		1/116 (0.9%)
Gastric ulcer	1/115 (0.9%)		0/116 (0%)
Gastric ulcer haemorrhage	1/115 (0.9%)		0/116 (0%)
Gastric varices haemorrhage	0/115 (0%)		1/116 (0.9%)
Gastrointestinal haemorrhage	3/115 (2.6%)		5/116 (4.3%)
Gastrooesophageal reflux disease	1/115 (0.9%)		0/116 (0%)
Haematemesis	0/115 (0%)		1/116 (0.9%)
Haemorrhoidal haemorrhage	0/115 (0%)		1/116 (0.9%)
Inguinal hernia	3/115 (2.6%)		1/116 (0.9%)
Oesophageal varices haemorrhage	7/115 (6.1%)		3/116 (2.6%)
Pancreatitis acute	1/115 (0.9%)		0/116 (0%)
Periodontitis	0/115 (0%)		1/116 (0.9%)
Umbilical hernia	2/115 (1.7%)		0/116 (0%)
Upper gastrointestinal haemorrhage	1/115 (0.9%)		0/116 (0%)
Varices oesophageal	0/115 (0%)		1/116 (0.9%)
Vomiting	1/115 (0.9%)		1/116 (0.9%)
General disorders
Death	0/115 (0%)		1/116 (0.9%)
Fatigue	1/115 (0.9%)		1/116 (0.9%)
Hernia	0/115 (0%)		1/116 (0.9%)
Oedema peripheral	1/115 (0.9%)		1/116 (0.9%)
Pitting oedema	1/115 (0.9%)		0/116 (0%)
Pyrexia	0/115 (0%)		1/116 (0.9%)
Hepatobiliary disorders
Biloma	0/115 (0%)		1/116 (0.9%)
Cholangitis	1/115 (0.9%)		0/116 (0%)
Cholecystitis chronic	0/115 (0%)		1/116 (0.9%)
Hepatic cirrhosis	1/115 (0.9%)		2/116 (1.7%)
Hepatic dysplasia	1/115 (0.9%)		0/116 (0%)
Hepatic failure	1/115 (0.9%)		2/116 (1.7%)
Hepatorenal syndrome	3/115 (2.6%)		1/116 (0.9%)
Jaundice	1/115 (0.9%)		1/116 (0.9%)
Jaundice cholestatic	0/115 (0%)		1/116 (0.9%)
Liver disorder	0/115 (0%)		1/116 (0.9%)
Infections and infestations
Arthritis bacterial	0/115 (0%)		2/116 (1.7%)
Bacteraemia	1/115 (0.9%)		1/116 (0.9%)
Bronchitis acute	0/115 (0%)		1/116 (0.9%)
Cellulitis	5/115 (4.3%)		1/116 (0.9%)
Dental caries	0/115 (0%)		1/116 (0.9%)
Gastroenteritis	2/115 (1.7%)		4/116 (3.4%)
Hepatitis B	0/115 (0%)		2/116 (1.7%)
Necrostising fasciitis	0/115 (0%)		1/116 (0.9%)
Otitis media chronic	1/115 (0.9%)		0/116 (0%)
Peritonitis bacterial	8/115 (7%)		7/116 (6%)
Pneumonia	1/115 (0.9%)		3/116 (2.6%)
Pulmonary tuberculosis	0/115 (0%)		1/116 (0.9%)
Pyelonephritis acute	1/115 (0.9%)		0/116 (0%)
Sepsis	8/115 (7%)		0/116 (0%)
Septic shock	3/115 (2.6%)		1/116 (0.9%)
Staphylococcal infection	1/115 (0.9%)		0/116 (0%)
Subdiaphragmatic abscess	1/115 (0.9%)		0/116 (0%)
Urinary tract infection	2/115 (1.7%)		3/116 (2.6%)
Viral infection	0/115 (0%)		1/116 (0.9%)
Injury, poisoning and procedural complications
Comminuted fracture	1/115 (0.9%)		0/116 (0%)
Post procedural haemorrhage	1/115 (0.9%)		0/116 (0%)
Investigations
Alpha 1 foetoprotein increased	0/115 (0%)		1/116 (0.9%)
Ammonia increased	1/115 (0.9%)		0/116 (0%)
Blood creatine phosphikinase increased	0/115 (0%)		1/116 (0.9%)
Blood pressure systolic	0/115 (0%)		1/116 (0.9%)
Transplant evaluation	0/115 (0%)		1/116 (0.9%)
Viral load increased	0/115 (0%)		1/116 (0.9%)
Metabolism and nutrition disorders
Dehydration	1/115 (0.9%)		2/116 (1.7%)
Diabetes mellitus	1/115 (0.9%)		0/116 (0%)
Diabetes mellitus inadequate control	0/115 (0%)		1/116 (0.9%)
Hyperglycaemia	0/115 (0%)		3/116 (2.6%)
Hypoglycaemia	0/115 (0%)		1/116 (0.9%)
Hyponatraemia	1/115 (0.9%)		0/116 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/115 (0%)		1/116 (0.9%)
Fracture nonunion	0/115 (0%)		1/116 (0.9%)
Myopathy	1/115 (0.9%)		0/116 (0%)
Pain in extremity	1/115 (0.9%)		0/116 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	0/115 (0%)		1/116 (0.9%)
Hepatic neoplasm	1/115 (0.9%)		0/116 (0%)
Hepatic neoplasm malignant	10/115 (8.7%)		12/116 (10.3%)
Nervous system disorders
Cerebellar infarction	1/115 (0.9%)		0/116 (0%)
Cerebral haemorrhage	1/115 (0.9%)		0/116 (0%)
Coma hepatic	0/115 (0%)		1/116 (0.9%)
Depressed level of consciousness	0/115 (0%)		2/116 (1.7%)
Encephalopathy	3/115 (2.6%)		2/116 (1.7%)
Hemiparesis	0/115 (0%)		1/116 (0.9%)
Hepatic encephalopathy	15/115 (13%)		13/116 (11.2%)
Renal and urinary disorders
Obstructive uropathy	1/115 (0.9%)		0/116 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/115 (0.9%)		0/116 (0%)
Postmenopausal haemorrhage	1/115 (0.9%)		0/116 (0%)
Proststitis	2/115 (1.7%)		0/116 (0%)
Uterine polyp	0/115 (0%)		1/116 (0.9%)
Vaginal Prolapse	0/115 (0%)		1/116 (0.9%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive airways disease	1/115 (0.9%)		0/116 (0%)
Epistaxis	1/115 (0.9%)		0/116 (0%)
Hydropneumothorax	0/115 (0%)		1/116 (0.9%)
Hydrothorax	1/115 (0.9%)		0/116 (0%)
Pleural effusion	5/115 (4.3%)		4/116 (3.4%)
Pneumonia aspiration	1/115 (0.9%)		0/116 (0%)
Surgical and medical procedures
Haemorrhoid operation	0/115 (0%)		1/116 (0.9%)
Vascular disorders
Arteriosclerosis	0/115 (0%)		1/116 (0.9%)
Haemorrhage	0/115 (0%)		1/116 (0.9%)
Hypotension	0/115 (0%)		1/116 (0.9%)
Hypovolaemic shock	0/115 (0%)		1/116 (0.9%)
Orthostatic hypotension	0/115 (0%)		1/116 (0.9%)
Shock	2/115 (1.7%)		0/116 (0%)
Other (Not Including Serious) Adverse Events
	Telbivudine 600 mg		Lamivudine 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/115 (86.1%)		97/116 (83.6%)
Blood and lymphatic system disorders
Anaemia	6/115 (5.2%)		7/116 (6%)
Splenomegaly	6/115 (5.2%)		7/116 (6%)
Gastrointestinal disorders
Abdominal discomfort	3/115 (2.6%)		10/116 (8.6%)
Abdominal distension	23/115 (20%)		14/116 (12.1%)
Abdominal pain	12/115 (10.4%)		14/116 (12.1%)
Abdominal pain upper	6/115 (5.2%)		10/116 (8.6%)
Ascites	40/115 (34.8%)		41/116 (35.3%)
Constipation	9/115 (7.8%)		9/116 (7.8%)
Diarrhoea	15/115 (13%)		16/116 (13.8%)
Dyspepsia	15/115 (13%)		12/116 (10.3%)
Nausea	10/115 (8.7%)		7/116 (6%)
Varices Oesophageal	6/115 (5.2%)		4/116 (3.4%)
Vomiting	8/115 (7%)		3/116 (2.6%)
General disorders
Asthenia	5/115 (4.3%)		12/116 (10.3%)
Fatigue	16/115 (13.9%)		14/116 (12.1%)
Oedema peripheral	33/115 (28.7%)		21/116 (18.1%)
Pitting oedema	13/115 (11.3%)		12/116 (10.3%)
Pyrexia	20/115 (17.4%)		17/116 (14.7%)
Hepatobiliary disorders
Jaundice	15/115 (13%)		11/116 (9.5%)
Infections and infestations
Nasopharyngitis	5/115 (4.3%)		9/116 (7.8%)
Upper respiratory tract infection	17/115 (14.8%)		12/116 (10.3%)
Investigations
Blood creatine phosphokinase increased	7/115 (6.1%)		2/116 (1.7%)
Metabolism and nutrition disorders
Anorexia	6/115 (5.2%)		3/116 (2.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/115 (6.1%)		10/116 (8.6%)
Back pain	10/115 (8.7%)		8/116 (6.9%)
Muscle cramp	6/115 (5.2%)		7/116 (6%)
Pain in extremity	6/115 (5.2%)		5/116 (4.3%)
Nervous system disorders
Dizziness	7/115 (6.1%)		9/116 (7.8%)
Encephalopathy	6/115 (5.2%)		6/116 (5.2%)
Headache	8/115 (7%)		11/116 (9.5%)
Hepatic Encephalopathy	7/115 (6.1%)		7/116 (6%)
Psychiatric disorders
Insomnia	11/115 (9.6%)		9/116 (7.8%)
Reproductive system and breast disorders
Gynaecomastia	16/115 (13.9%)		19/116 (16.4%)
Respiratory, thoracic and mediastinal disorders
Cough	17/115 (14.8%)		8/116 (6.9%)
Dyspnoea	6/115 (5.2%)		5/116 (4.3%)
Epistaxis	7/115 (6.1%)		4/116 (3.4%)
Skin and subcutaneous tissue disorders
Pruritus	10/115 (8.7%)		12/116 (10.3%)
Spider Naevus	6/115 (5.2%)		2/116 (1.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.