Trial Outcomes & Findings for Adefovir Dipivoxil For The Treatment Of Patients With Chronic Hepatitis B Related Advanced Fibrosis Or Cirrhosis (NCT NCT00347009)

NCT ID: NCT00347009

Last Updated: 2012-06-04

Results Overview

The Ishak fibrosis score is a scoring system (ranging from 0 to 6) that measures the degree of fibrosis (scarring) of the liver, which is caused by chronic necroinflammation (an inflammatory process in the liver including or leading to death of liver cells). A score of 0 represents no fibrosis, and a score of 6 represents established cirrhosis. Participants were classified as improved if the Ishak fibrosis score at Month 36 was 1 or more points less from the Screening score.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 155 participants
• Primary outcome timeframe: Screening and Month 36
• Results posted on: 2012-06-04

Participant Flow

Participant milestones

Measure	Adefovir Dipivoxil 10 Milligrams (mg) Adefovir Dipivoxil 10 mg, once daily
Overall Study STARTED	155
Overall Study COMPLETED	128
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Measure	Adefovir Dipivoxil 10 Milligrams (mg) Adefovir Dipivoxil 10 mg, once daily
Overall Study Death	1
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	3
Overall Study Physician Decision	5
Overall Study Lost to Follow-up	4
Overall Study Protocol Violation	2
Overall Study Adverse Laboratory Experience	1
Overall Study Insufficient Viral Suppression	3
Overall Study Increased ALT/HBV DNA	1
Overall Study Serious Adverse Event	1

Baseline Characteristics

Adefovir Dipivoxil For The Treatment Of Patients With Chronic Hepatitis B Related Advanced Fibrosis Or Cirrhosis

Baseline characteristics by cohort

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Age Continuous	47.7 Years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants
Sex: Female, Male Male	116 Participants n=5 Participants
Race/Ethnicity, Customized Asian	155 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants
Time since Diagnosis of Chronic Hepatitis B	11.29 years STANDARD_DEVIATION 8.40 • n=5 Participants

PRIMARY outcome

Timeframe: Screening and Month 36

Population: Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication, regardless of whether the participants completed the planned duration of the study

The Ishak fibrosis score is a scoring system (ranging from 0 to 6) that measures the degree of fibrosis (scarring) of the liver, which is caused by chronic necroinflammation (an inflammatory process in the liver including or leading to death of liver cells). A score of 0 represents no fibrosis, and a score of 6 represents established cirrhosis. Participants were classified as improved if the Ishak fibrosis score at Month 36 was 1 or more points less from the Screening score.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With Histologic Improvement at Month 36 (Intent-to-Treat Population)	52 participants

PRIMARY outcome

Timeframe: Screening and Month 36

Population: Per Protocol (PP) Population: all participants in the ITT Population with interpretable liver biopsies at baseline and at the 36-month follow-up visit and without major violations of the protocol

The Ishak fibrosis score is a scoring system (ranging from 0 to 6) that measures the degree of fibrosis (scarring) of the liver, which is caused by chronic necroinflammation (an inflammatory process in the liver including or leading to death of liver cells). A score of 0 represents no fibrosis, and a score of 6 represents established cirrhosis. Participants were classified as improved if the Ishak fibrosis score at Month 36 was 1 or more points less from the Screening score.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=114 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With Histologic Improvement at Month 36 (Per Protocol Population)	52 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

The Child-Pugh score (modified version for scoring prothrombin time against reference range) was used in the study to assess the prognosis of chronic liver disease, mainly cirrhosis. The score employs five clinical measures of liver disease: encephalopathy, ascites, albumin, prothrombin time, and bilirubin. Each measure is scored on a scale of 1-3, with 1 being normal and 3 indicating most severe derangement. The total score for the Child-Pugh assessment was calculated as the sum of the 5 contributing scores, with a score range of 5 (best prognosis) to 15 (worst prognosis).

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With a Reduction From Baseline in the Child-Pugh Score by 2 Points or More at Months 12, 24, and 36 Month 12	0 participants
Number of Participants With a Reduction From Baseline in the Child-Pugh Score by 2 Points or More at Months 12, 24, and 36 Month 24	2 participants
Number of Participants With a Reduction From Baseline in the Child-Pugh Score by 2 Points or More at Months 12, 24, and 36 Month 36	1 participants

SECONDARY outcome

Timeframe: Screening and Month 36

Population: ITT Population

The Knodell scoring system, also called the Histologic Activity Index (HAI), classifies liver biopsy specimens according to scores into 4 categories of histologic features: (I) periportal and/or bridging necrosis (scores from 0 to 10); (II) intralobular degeneration and focal necrosis (scores from 0 to 4); (III) portal inflammation (scores from 0 to 4); (IV) fibrosis (scores from 0 to 4). The Knodell necroinflammation score is the sum of scores from Parts I-III, hence a range of 0 to 18, and measures the degree of acute necroinflammatory activity in the liver.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With a Reduction From Screening of at Least 2 Points in the Knodell Necroinflammation Score at Month 36	64 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

The levels of HBV DNA in serum were measured using the Amplicor Cobas assay by Roche Diagnostics (detection limit 300 copies/milliliter [ml]). Changes from baseline in the serum HBV DNA level at Months 12, 24 and 36 were calculated as Month 12 minus baseline, Month 24 minus baseline, and Month 36 minus baseline respectively. Change is reported in log10 units.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Change From Baseline in Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level at Months 12, 24, and 36 Month 12	-4.557 log10 copies/ml Standard Deviation 1.639
Change From Baseline in Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level at Months 12, 24, and 36 Month 24	-4.536 log10 copies/ml Standard Deviation 2.115
Change From Baseline in Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level at Months 12, 24, and 36 Month 36	-4.454 log10 copies/ml Standard Deviation 2.436

SECONDARY outcome

Timeframe: Months 12, 24, and 36

Population: ITT Population

Virological response was defined as an HBV DNA level <= 10^3 copies/ml.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^3 Copies/ml) at Months 12, 24, and 36 Month 12	91 participants
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^3 Copies/ml) at Months 12, 24, and 36 Month 24	99 participants
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^3 Copies/ml) at Months 12, 24, and 36 Month 36	102 participants

SECONDARY outcome

Timeframe: Months 12, 24, and 36

Population: ITT Population

Virological response was defined as an HBV DNA level <= 10^4 copies/ml.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^4 Copies/ml) at Months 12, 24, and 36 Month 12	110 participants
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^4 Copies/ml) at Months 12, 24, and 36 Month 24	114 participants
Number of Participants Achieving Virological Response (HBV DNA Level <= 10^4 Copies/ml) at Months 12, 24, and 36 Month 36	109 participants

SECONDARY outcome

Timeframe: Months 12, 24, and 36

Population: ITT Population

Undetectable HBV DNA was defined as an HBV DNA level below the lower limit of detection (LLOD) of 300 copies/ml.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With Undetectable HBV DNA at Months 12, 24, and 36 Month 12	83 participants
Number of Participants With Undetectable HBV DNA at Months 12, 24, and 36 Month 24	95 participants
Number of Participants With Undetectable HBV DNA at Months 12, 24, and 36 Month 36	90 participants

SECONDARY outcome

Timeframe: Months 12, 24, and 36

Population: ITT Population

Virological breakthrough was defined as an increase in serum HBV DNA levels by more than 1 log10 copies/ml from treatment nadir, i.e., the lowest HBV DNA value during the study.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With Virological Breakthrough at Months 12, 24, and 36 Month 24	16 participants
Number of Participants With Virological Breakthrough at Months 12, 24, and 36 Month 36	21 participants
Number of Participants With Virological Breakthrough at Months 12, 24, and 36 Month 12	3 participants

SECONDARY outcome

Timeframe: Months 12, 24, and 36

Population: ITT Population

ALT levels were measured as part of the liver function tests. Participants with ALT normalization at each visit were defined as those with a value below the upper limit of the normal (ULN) range for ALT provided by that site at the respective visit.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Months 12, 24, and 36 Month 12	87 participants
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Months 12, 24, and 36 Month 24	91 participants
Number of Participants With Alanine Aminotransferase (ALT) Normalization at Months 12, 24, and 36 Month 36	91 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

HBeAg positive was defined as the presence of a detectable level of HBeAg.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Who Were Hepatitis B Envelope Antigen (HBeAg) Positive at Baseline and Developed Undetectable Levels of HBeAg at Months 12, 24, and 36 Month 12	17 participants
Number of Participants Who Were Hepatitis B Envelope Antigen (HBeAg) Positive at Baseline and Developed Undetectable Levels of HBeAg at Months 12, 24, and 36 Month 24	27 participants
Number of Participants Who Were Hepatitis B Envelope Antigen (HBeAg) Positive at Baseline and Developed Undetectable Levels of HBeAg at Months 12, 24, and 36 Month 36	28 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

HBeAg seroconversion was defined as a decrease in HBeAg to undetectable levels and a gain of detectable levels of Hepatitis B envelope antibody (HBeAb).

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Who Were HBeAg Positive at Baseline, With HBeAg Seroconversion at Months 12, 24, and 36 Month 12	10 participants
Number of Participants Who Were HBeAg Positive at Baseline, With HBeAg Seroconversion at Months 12, 24, and 36 Month 24	18 participants
Number of Participants Who Were HBeAg Positive at Baseline, With HBeAg Seroconversion at Months 12, 24, and 36 Month 36	15 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

HBsAg positive was defined as the presence of a detectable level of HBsAg.

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Who Were Hepatitis B Surface Antigen (HBsAg) Positive at Baseline and Developed Undetectable Levels of HBsAg at Months 12, 24, and 36 Month 12	0 participants
Number of Participants Who Were Hepatitis B Surface Antigen (HBsAg) Positive at Baseline and Developed Undetectable Levels of HBsAg at Months 12, 24, and 36 Month 24	0 participants
Number of Participants Who Were Hepatitis B Surface Antigen (HBsAg) Positive at Baseline and Developed Undetectable Levels of HBsAg at Months 12, 24, and 36 Month 36	0 participants

SECONDARY outcome

Timeframe: Baseline and Months 12, 24, and 36

Population: ITT Population

HBsAg seroconversion was defined as a decrease in HBsAg to undetectable levels and a gain of detectable levels of Hepatitis B surface antibody (HBsAb).

Outcome measures

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 Participants Adefovir Dipivoxil 10 mg, once daily
Number of Participants Who Were HBsAg Positive at Baseline, With HBsAg Seroconversion at Months 12, 24, and 36 Month 12	0 participants
Number of Participants Who Were HBsAg Positive at Baseline, With HBsAg Seroconversion at Months 12, 24, and 36 Month 24	0 participants
Number of Participants Who Were HBsAg Positive at Baseline, With HBsAg Seroconversion at Months 12, 24, and 36 Month 36	0 participants

Adverse Events

Adefovir Dipivoxil 10 Milligrams (mg)

Serious events: 20 serious events

Other events: 99 other events

Deaths: 0 deaths

Serious adverse events

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 participants at risk Adefovir Dipivoxil 10 mg, once daily
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	4.5% 7/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant recurrent	1.3% 2/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellar tumour	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Duodenal ulcer	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Inguinal hernia	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Oesophageal obstruction	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Injury, poisoning and procedural complications Excoriation	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Injury, poisoning and procedural complications Femur fracture	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Injury, poisoning and procedural complications Ribs fracture	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Injury, poisoning and procedural complications Wrist fracture	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Acute sinusitis	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Appendicitis	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Hepatitis B	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Periorbital cellulitis	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Pneumonia bacterial	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Hepatobiliary disorders Bile duct stone	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Hepatobiliary disorders Cholangitis	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Hepatobiliary disorders Jaundice cholestatic	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Nervous system disorders Hepatic encephalopathy	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Nervous system disorders Presyncope	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Psychiatric disorders Depression	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Psychiatric disorders Suicide attempt	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Renal and urinary disorders Diabetic nephropathy	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Respiratory, thoracic and mediastinal disorders Haemothorax	1.3% 2/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.65% 1/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.

Other adverse events

Measure	Adefovir Dipivoxil 10 Milligrams (mg) n=155 participants at risk Adefovir Dipivoxil 10 mg, once daily
Gastrointestinal disorders Abdominal pain upper	9.7% 15/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Diarrhoea	7.1% 11/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Abdominal distension	6.5% 10/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Gastrointestinal disorders Gastritis	5.8% 9/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Infections and infestations Upper respiratory tract infection	25.8% 40/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Musculoskeletal and connective tissue disorders Back pain	7.7% 12/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Respiratory, thoracic and mediastinal disorders Cough	10.3% 16/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.8% 9/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
General disorders Fatigue	8.4% 13/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Investigations Alanine aminotransferase increased	16.8% 26/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Investigations Aspartate aminotransferase increased	14.8% 23/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Investigations Hepatitis B DNA increased	5.8% 9/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Investigations Alpha 1 fetoprotein increased	5.2% 8/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Skin and subcutaneous tissue disorders Pruritus	6.5% 10/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Nervous system disorders Headache	5.2% 8/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Psychiatric disorders Insomnia	5.2% 8/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.
Vascular disorders Hypertension	5.2% 8/155 • Screening to Month 42 Adverse events (AEs) were reported spontaneously by the participant or determined by the investigator through questioning the participant in a general way; the severity, outcome and cause of each reported AE were assessed and recorded.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER