Trial Outcomes & Findings for Telbivudine Versus Lamivudine in Adults With Decompensated Chronic Hepatitis B and Evidence of Cirrhosis (NCT NCT00076336)

Last Updated: 2011-09-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

232 participants

Primary outcome timeframe

From Baseline to Week 52

Results posted on

2011-09-05

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Telbivudine 600 mg 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.	Lamivudine 100 mg 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.
Overall Study STARTED	116	116
Overall Study Safety Population	115	116
Overall Study Intent to Treat (ITT) Population	114	114
Overall Study Completed Week 52	97	94
Overall Study Completed Week 104	70	62
Overall Study COMPLETED	64	60
Overall Study NOT COMPLETED	52	56

Reasons for withdrawal

Reasons for withdrawal
Measure	Telbivudine 600 mg 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.	Lamivudine 100 mg 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.
Overall Study Death	13	17
Overall Study Adverse Event	4	4
Overall Study Lost to Follow-up	4	4
Overall Study Non-Compliance	2	0
Overall Study Creatinine Clearance < 30 or Dialysis	0	1
Overall Study Patient, Investigator, Sponsor request	8	6
Overall Study Liver Transplantation	3	3
Overall Study Virologic Breakthrough	14	16
Overall Study Treatment failure	4	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Telbivudine 600 mg n=114 Participants 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.	Lamivudine 100 mg n=114 Participants 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 n=228 Participants Total of all reporting groups
Age Continuous	49.6 years STANDARD_DEVIATION 10.88 • n=5 Participants	51.9 years STANDARD_DEVIATION 9.98 • n=7 Participants	50.8 years STANDARD_DEVIATION 10.48 • n=5 Participants
Age, Customized < 30 years	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Age, Customized Between 30 and 50 years	44 Participants n=5 Participants	44 Participants n=7 Participants	88 Participants n=5 Participants
Age, Customized > 50 years	64 Participants n=5 Participants	68 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	33 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	81 Participants n=7 Participants	168 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 52

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

Outcome measures

Outcome measures
Measure	Telbivudine 600 mg n=114 Participants 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.	Lamivudine 100 mg n=114 Participants 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.
Number of Participants With Clinical Response Clinical Response	65 Participants	62 Participants
Number of Participants With Clinical Response HBV DNA < 4log10copies/mL	85 Participants	82 Participants
Number of Participants With Clinical Response Normal ALT	78 Participants	81 Participants
Number of Participants With Clinical Response Improvement/stabilization in CTP	96 Participants	96 Participants
Number of Participants With Clinical Response Improvement in CTP (reduction ≥ 2)	34 Participants	43 Participants
Number of Participants With Clinical Response Stabilization in CTP (absolute change ≤ 1)	56 Participants	48 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 104

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

Time to Clinical Response defined as the number of days elapsed from the baseline visit to achieving initial Clinical Response.

Outcome measures

Outcome measures
Measure	Telbivudine 600 mg n=95 Participants 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.	Lamivudine 100 mg n=92 Participants 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.
Time to Initial Clinical Response	137.5 Days Standard Deviation 126.14	125.2 Days Standard Deviation 111.24

SECONDARY outcome

Timeframe: Baseline to Week 104

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

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.

Outcome measures

Outcome measures
Measure	Telbivudine 600 mg n=95 Participants 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.	Lamivudine 100 mg n=92 Participants 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.
Duration of Initial Clinical Response	473.1 Days Standard Error 26.13	456.3 Days Standard Error 24.97

SECONDARY outcome

Timeframe: From Baseline to weeks 52 and 104

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Telbivudine 600 mg n=114 Participants 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.	Lamivudine 100 mg n=114 Participants 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.
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Worsening At Week 104	28 Participants	30 Participants
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Improvement At Week 52	36 Participants	44 Participants
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Stabilization At Week 52	60 Participants	52 Participants
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Worsening At Week 52	18 Participants	18 Participants
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Improvement At Week 104	44 Participants	46 Participants
Number of Participants With Improvement, Stabilization, and Worsening in Child-Turcotte-Pugh (CTP) Score at Week 52 and Week 104 Stabilization At Week 104	42 Participants	38 Participants

SECONDARY outcome

Timeframe: Baseline and Week 104

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Telbivudine 600 mg n=114 Participants 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.	Lamivudine 100 mg n=114 Participants 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.
Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score Improvement at Week 104	30 Participants	31 Participants
Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score Stabilization at Week 104	57 Participants	54 Participants
Number of Participants With Improvement, Stabilization, and Worsening in a Modified (3-component) CTP Score Worsening at Week 104	27 Participants	29 Participants

Adverse Events

Telbivudine 600 mg

Serious events: 59 serious events

Other events: 99 other events

Deaths: 0 deaths

Lamivudine 100 mg

Serious events: 68 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Telbivudine 600 mg n=115 participants at risk 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.	Lamivudine 100 mg n=116 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.00% 0/115 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.	0.86% 1/116 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.
Cardiac disorders Sinus bradycardia	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Abdominal pain	1.7% 2/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Abdominal pain upper	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Abdominal strangulated hernia	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Ascites	9.6% 11/115 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.	1.7% 2/116 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.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Duodenal ulcer haemorrage	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Enteritis	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Food poisoning	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Gastric ulcer	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Gastric varices haemorrhage	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.6% 3/115 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.	4.3% 5/116 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Haematemesis	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Inguinal hernia	2.6% 3/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Oesophageal varices haemorrhage	6.1% 7/115 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.	2.6% 3/116 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.
Gastrointestinal disorders Pancreatitis acute	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Periodontitis	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Umbilical hernia	1.7% 2/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.87% 1/115 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.	0.00% 0/116 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.
Gastrointestinal disorders Varices oesophageal	0.00% 0/115 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.	0.86% 1/116 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.
Gastrointestinal disorders Vomiting	0.87% 1/115 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.	0.86% 1/116 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.
General disorders Death	0.00% 0/115 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.	0.86% 1/116 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.
General disorders Fatigue	0.87% 1/115 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.	0.86% 1/116 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.
General disorders Hernia	0.00% 0/115 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.	0.86% 1/116 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.
General disorders Oedema peripheral	0.87% 1/115 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.	0.86% 1/116 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.
General disorders Pitting oedema	0.87% 1/115 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.	0.00% 0/116 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.
General disorders Pyrexia	0.00% 0/115 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.	0.86% 1/116 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.
Hepatobiliary disorders Biloma	0.00% 0/115 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.	0.86% 1/116 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.
Hepatobiliary disorders Cholangitis	0.87% 1/115 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.	0.00% 0/116 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.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/115 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.	0.86% 1/116 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.
Hepatobiliary disorders Hepatic cirrhosis	0.87% 1/115 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.	1.7% 2/116 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.
Hepatobiliary disorders Hepatic dysplasia	0.87% 1/115 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.	0.00% 0/116 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.
Hepatobiliary disorders Hepatic failure	0.87% 1/115 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.	1.7% 2/116 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.
Hepatobiliary disorders Hepatorenal syndrome	2.6% 3/115 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.	0.86% 1/116 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.
Hepatobiliary disorders Jaundice	0.87% 1/115 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.	0.86% 1/116 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.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/115 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.	0.86% 1/116 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.

Other adverse events
Measure	Telbivudine 600 mg n=115 participants at risk 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.	Lamivudine 100 mg n=116 participants at risk 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.
Blood and lymphatic system disorders Anaemia	5.2% 6/115 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.	6.0% 7/116 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.
Blood and lymphatic system disorders Splenomegaly	5.2% 6/115 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.	6.0% 7/116 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.
Gastrointestinal disorders Abdominal discomfort	2.6% 3/115 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.	8.6% 10/116 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.
Gastrointestinal disorders Abdominal distension	20.0% 23/115 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.	12.1% 14/116 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.
Gastrointestinal disorders Abdominal pain	10.4% 12/115 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.	12.1% 14/116 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.
Gastrointestinal disorders Abdominal pain upper	5.2% 6/115 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.	8.6% 10/116 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.
Gastrointestinal disorders Ascites	34.8% 40/115 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.	35.3% 41/116 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.
Gastrointestinal disorders Constipation	7.8% 9/115 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.	7.8% 9/116 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.
Gastrointestinal disorders Diarrhoea	13.0% 15/115 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.	13.8% 16/116 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.
Gastrointestinal disorders Dyspepsia	13.0% 15/115 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.	10.3% 12/116 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.
Gastrointestinal disorders Nausea	8.7% 10/115 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.	6.0% 7/116 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.
Gastrointestinal disorders Varices Oesophageal	5.2% 6/115 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.	3.4% 4/116 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.
Gastrointestinal disorders Vomiting	7.0% 8/115 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.	2.6% 3/116 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.
General disorders Asthenia	4.3% 5/115 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.	10.3% 12/116 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.
General disorders Fatigue	13.9% 16/115 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.	12.1% 14/116 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.
General disorders Oedema peripheral	28.7% 33/115 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.	18.1% 21/116 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.
General disorders Pitting oedema	11.3% 13/115 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.	10.3% 12/116 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.
General disorders Pyrexia	17.4% 20/115 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.	14.7% 17/116 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.
Hepatobiliary disorders Jaundice	13.0% 15/115 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.	9.5% 11/116 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.
Infections and infestations Nasopharyngitis	4.3% 5/115 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.	7.8% 9/116 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.
Infections and infestations Upper respiratory tract infection	14.8% 17/115 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.	10.3% 12/116 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.
Investigations Blood creatine phosphokinase increased	6.1% 7/115 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.	1.7% 2/116 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.
Metabolism and nutrition disorders Anorexia	5.2% 6/115 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.	2.6% 3/116 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.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 7/115 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.	8.6% 10/116 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.
Musculoskeletal and connective tissue disorders Back pain	8.7% 10/115 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.	6.9% 8/116 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.
Musculoskeletal and connective tissue disorders Muscle cramp	5.2% 6/115 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.	6.0% 7/116 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.
Musculoskeletal and connective tissue disorders Pain in extremity	5.2% 6/115 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.	4.3% 5/116 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.
Nervous system disorders Dizziness	6.1% 7/115 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.	7.8% 9/116 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.
Nervous system disorders Encephalopathy	5.2% 6/115 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.	5.2% 6/116 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.
Nervous system disorders Headache	7.0% 8/115 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.	9.5% 11/116 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.
Nervous system disorders Hepatic Encephalopathy	6.1% 7/115 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.	6.0% 7/116 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.
Psychiatric disorders Insomnia	9.6% 11/115 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.	7.8% 9/116 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.
Reproductive system and breast disorders Gynaecomastia	13.9% 16/115 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.	16.4% 19/116 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.
Respiratory, thoracic and mediastinal disorders Cough	14.8% 17/115 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.	6.9% 8/116 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.2% 6/115 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.	4.3% 5/116 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.1% 7/115 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.	3.4% 4/116 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.
Skin and subcutaneous tissue disorders Pruritus	8.7% 10/115 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.	10.3% 12/116 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.
Skin and subcutaneous tissue disorders Spider Naevus	5.2% 6/115 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.	1.7% 2/116 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.