Trial Outcomes & Findings for Effect of Risk Factors Likely to Influence Immuno of Combined Hepatitis A & B Vacc vs Monovalent Hepatitis A & B Vacc (NCT NCT00289731)

NCT ID: NCT00289731

Last Updated: 2019-11-15

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

596 participants

Primary outcome timeframe

At Month 7 after Twinrix vaccination

Results posted on

2019-11-15

Participant Flow

A total of 596 subjects (199 in Twinrix Group, 200 in Engerix-B+Havrix Group and 197 in HB VAX PRO+Vaqta Group) were enrolled and vaccinated in the study.

Participant milestones

Participant milestones
Measure	Twinrix Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Overall Study STARTED	199	200	197
Overall Study COMPLETED	197	198	195
Overall Study NOT COMPLETED	2	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Twinrix Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Overall Study Adverse Event	1	2	2
Overall Study Other	1	0	0

Baseline Characteristics

Effect of Risk Factors Likely to Influence Immuno of Combined Hepatitis A & B Vacc vs Monovalent Hepatitis A & B Vacc

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Twinrix Group n=199 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=200 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=197 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	Total n=596 Participants Total of all reporting groups
Age, Continuous	55.2 Years STANDARD_DEVIATION 9.24 • n=5 Participants	55.3 Years STANDARD_DEVIATION 9.91 • n=7 Participants	55.0 Years STANDARD_DEVIATION 9.64 • n=5 Participants	55.17 Years STANDARD_DEVIATION 9.59 • n=4 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	100 Participants n=7 Participants	101 Participants n=5 Participants	298 Participants n=4 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	100 Participants n=7 Participants	96 Participants n=5 Participants	298 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	199 Participants n=5 Participants	200 Participants n=7 Participants	196 Participants n=5 Participants	595 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Month 7 after Twinrix vaccination

Population: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all subjects who met all eligibility criteria and for whom data concerning immunogenicity endpoint measures were available.

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Antibody Concentrations for Anti-hepatitis A Virus (Anti-HAV) and Anti-hepatitis B Surface (Anti-HBs) Antigens Anti-HAV	2746.5 mIU/mL Interval 2256.3 to 3343.2	—	—
Antibody Concentrations for Anti-hepatitis A Virus (Anti-HAV) and Anti-hepatitis B Surface (Anti-HBs) Antigens Anti-HBs	1153.9 mIU/mL Interval 829.8 to 1604.7	—	—

PRIMARY outcome

Timeframe: At Month 7

Population: The analysis was performed on the ATP cohort for immunogenicity, which included all subjects who met all eligibility criteria and for whom data concerning immunogenicity endpoint measures were available.

Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration ≥ 15mIU/mL; seropositivity for anti-HBs antibodies was defined as anti-HBs antibody concentration ≥ 3.3 mIU/mL.

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HAV	176 Participants	180 Participants	174 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HBs	168 Participants	152 Participants	137 Participants

PRIMARY outcome

Timeframe: At Month 7

A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL.

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen	166 Participants	145 Participants	125 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=168 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=165 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HBs	491.2 mIU/mL Interval 342.3 to 704.9	179.1 mIU/mL Interval 128.5 to 249.7	—
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HAV	1394.3 mIU/mL Interval 1159.8 to 1676.1	3707.2 mIU/mL Interval 3081.4 to 4460.2	—

SECONDARY outcome

Timeframe: At Month 7

Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by gender (females and males).

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Gender Anti-HAV, Females	86 Participants	88 Participants	89 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Gender Anti-HAV, Males	90 Participants	92 Participants	85 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Gender Anti-HBs, Females	82 Participants	77 Participants	78 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Gender Anti-HBs, Males	86 Participants	75 Participants	59 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HAV, ≤ 50 YOA	58 Participants	59 Participants	59 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HAV, 51-60 YOA	63 Participants	63 Participants	57 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HAV, ≥ 61 YOA	55 Participants	58 Participants	58 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HBs, ≤ 50 YOA	57 Participants	50 Participants	54 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HBs, 51-60 YOA	63 Participants	58 Participants	46 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age Anti-HBs, ≥ 61 YOA	48 Participants	44 Participants	37 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HAV, Healthy	57 Participants	61 Participants	58 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HAV, Overweight	66 Participants	63 Participants	58 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HAV, Obese	53 Participants	56 Participants	58 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HBs, Healthy	53 Participants	54 Participants	48 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HBs, Overweight	62 Participants	53 Participants	44 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI) Anti-HBs, Obese	53 Participants	45 Participants	45 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Smoking Status Anti-HAV, Smokers	50 Participants	51 Participants	32 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Smoking Status Anti-HAV, Non-smokers	126 Participants	129 Participants	142 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Smoking Status Anti-HBs, Smokers	47 Participants	44 Participants	23 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Smoking Status Anti-HBs, Non-smokers	121 Participants	108 Participants	114 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HAV, None or Mild	108 Participants	105 Participants	100 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HAV, Moderate	55 Participants	67 Participants	62 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HAV, Heavy	13 Participants	8 Participants	12 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HBs, None or Mild	105 Participants	89 Participants	80 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HBs, Moderate	52 Participants	57 Participants	47 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption Anti-HBs, Heavy	11 Participants	6 Participants	10 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Concomitant Medication Anti-HAV, Concomitant medication	160 Participants	167 Participants	160 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Concomitant Medication Anti-HAV, No concomitant medication	16 Participants	13 Participants	14 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Concomitant Medication Anti-HBs, Concomitant medication	153 Participants	141 Participants	127 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Concomitant Medication Anti-HBs, No concomitant medication	15 Participants	11 Participants	10 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HAV,No Medical condition	24 Participants	20 Participants	20 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HAV,Past Medical condition	13 Participants	22 Participants	15 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HAV,Current Medical condition	139 Participants	138 Participants	139 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HBs,No Medical condition	23 Participants	19 Participants	15 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HBs,Past Medical condition	13 Participants	18 Participants	12 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition Anti-HBs,Current Medical condition	132 Participants	115 Participants	110 Participants

SECONDARY outcome

Timeframe: At Month 7

A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by gender (females and males).

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Gender Females	82 Participants	73 Participants	75 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Gender Males	84 Participants	72 Participants	50 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Age ≤ 50 YOA	57 Participants	48 Participants	52 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Age 51-60 YOA	63 Participants	55 Participants	43 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Age ≥ 61 YOA	46 Participants	42 Participants	30 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by BMI Healthy	52 Participants	51 Participants	46 Participants
Number of Seroprotected Subjects Against HBs Antigen, by BMI Overweight	62 Participants	51 Participants	40 Participants
Number of Seroprotected Subjects Against HBs Antigen, by BMI Obese	52 Participants	43 Participants	39 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Smoking Status Smokers	47 Participants	42 Participants	22 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Smoking Status Non-smokers	119 Participants	103 Participants	103 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Alcohol Consumption None or Mild	105 Participants	87 Participants	76 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Alcohol Consumption Moderate	50 Participants	52 Participants	41 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Alcohol Consumption Heavy	11 Participants	6 Participants	8 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Concomitant Medication Concomitant medication	151 Participants	135 Participants	117 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Concomitant Medication No concomitant medication	15 Participants	10 Participants	8 Participants

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against HBs Antigen, by Medical Condition Past medical condition	13 Participants	18 Participants	12 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Medical Condition No medical condition	23 Participants	18 Participants	13 Participants
Number of Seroprotected Subjects Against HBs Antigen, by Medical Condition Current medical condition	130 Participants	109 Participants	100 Participants

SECONDARY outcome

Timeframe: At Month 7

Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by gender (females and males).

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Gender Anti-HBs, Females	1957.5 mIU/mL Interval 1295.2 to 2958.4	474.2 mIU/mL Interval 274.8 to 818.3	273.8 mIU/mL Interval 182.0 to 411.7
Anti-HAV and Anti-HBs Antibody Concentrations, by Gender Anti-HAV, Females	2968.1 mIU/mL Interval 2176.3 to 4047.9	2089.2 mIU/mL Interval 1618.6 to 2696.6	5307.0 mIU/mL Interval 4224.5 to 6666.7
Anti-HAV and Anti-HBs Antibody Concentrations, by Gender Anti-HAV, Males	2550.3 mIU/mL Interval 1986.6 to 3273.8	947.0 mIU/mL Interval 742.2 to 1208.4	2546.4 mIU/mL Interval 1932.2 to 3355.8
Anti-HAV and Anti-HBs Antibody Concentrations, by Gender Anti-HBs, Males	697.1 mIU/mL Interval 425.2 to 1142.9	509.4 mIU/mL Interval 314.0 to 826.5	102.2 mIU/mL Interval 60.1 to 173.8

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HAV, ≤ 50 YOA	4034.0 mIU/mL Interval 2927.7 to 5558.4	1769.8 mIU/mL Interval 1301.1 to 2407.3	5166.9 mIU/mL Interval 3995.2 to 6682.2
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HAV, 51-60 YOA	2521.6 mIU/mL Interval 1847.4 to 3441.7	1714.8 mIU/mL Interval 1286.3 to 2286.0	3822.8 mIU/mL Interval 2698.0 to 5416.4
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HAV, ≥ 61 YOA	2019.4 mIU/mL Interval 1368.1 to 2980.9	873.8 mIU/mL Interval 616.7 to 1237.9	2566.2 mIU/mL Interval 1822.0 to 3614.4
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HBs, ≤ 50 YOA	1839.9 mIU/mL Interval 1042.0 to 3248.9	753.7 mIU/mL Interval 393.7 to 1443.1	217.2 mIU/mL Interval 126.1 to 374.0
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HBs, 51-60 YOA	986.4 mIU/mL Interval 583.1 to 1668.7	324.1 mIU/mL Interval 182.6 to 575.3	286.6 mIU/mL Interval 165.0 to 497.7
Anti-HAV and Anti-HBs Antibody Concentrations, by Age Anti-HBs, ≥ 61 YOA	814.6 mIU/mL Interval 425.2 to 1560.6	522.6 mIU/mL Interval 262.7 to 1039.4	75.3 mIU/mL Interval 40.9 to 138.6

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HAV, Healthy	3565.4 mIU/mL Interval 2509.8 to 5065.1	1569.2 mIU/mL Interval 1115.1 to 2208.4	4756.2 mIU/mL Interval 3399.5 to 6654.5
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HAV, Overweight	2846.6 mIU/mL Interval 2140.2 to 3786.3	1663.9 mIU/mL Interval 1252.7 to 2210.1	3943.9 mIU/mL Interval 2784.3 to 5586.4
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HAV, Obese	1984.0 mIU/mL Interval 1327.6 to 2964.9	1004.8 mIU/mL Interval 718.8 to 1404.5	2716.2 mIU/mL Interval 2065.6 to 3571.8
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HBs, Healthy	2140.5 mIU/mL Interval 1168.9 to 3919.6	505.4 mIU/mL Interval 274.1 to 931.8	475.2 mIU/mL Interval 278.9 to 809.7
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HBs, Overweight	1540.8 mIU/mL Interval 889.1 to 2670.2	609.4 mIU/mL Interval 338.2 to 1097.9	165.9 mIU/mL Interval 91.5 to 300.9
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI Anti-HBs, Obese	443.5 mIU/mL Interval 268.5 to 732.7	368.3 mIU/mL Interval 178.2 to 761.4	68.1 mIU/mL Interval 41.9 to 110.7

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Smoking Status Anti-HAV, Smokers	1844.6 mIU/mL Interval 1233.7 to 2758.0	1433.2 mIU/mL Interval 1012.9 to 2028.0	3456.0 mIU/mL Interval 2363.5 to 5053.4
Anti-HAV and Anti-HBs Antibody Concentrations, by Smoking Status Anti-HAV, Non-Smokers	3216.5 mIU/mL Interval 2578.8 to 4012.0	1379.2 mIU/mL Interval 1106.8 to 1718.6	3766.3 mIU/mL Interval 3047.8 to 4654.3
Anti-HAV and Anti-HBs Antibody Concentrations, by Smoking Status Anti-HBs, Smokers	654.4 mIU/mL Interval 358.8 to 1193.6	416.4 mIU/mL Interval 204.4 to 848.2	108.1 mIU/mL Interval 52.2 to 223.5
Anti-HAV and Anti-HBs Antibody Concentrations, by Smoking Status Anti-HBs, Non-smokers	1438.3 mIU/mL Interval 972.0 to 2128.5	525.5 mIU/mL Interval 343.7 to 803.2	198.3 mIU/mL Interval 136.6 to 288.0

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HAV, None or Mild	2505.1 mIU/mL Interval 1912.9 to 3280.7	1403.6 mIU/mL Interval 1084.9 to 1816.0	3731.1 mIU/mL Interval 2897.6 to 4804.2
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HAV, Moderate	3174.6 mIU/mL Interval 2314.9 to 4353.6	1453.8 mIU/mL Interval 1115.5 to 1894.7	3754.3 mIU/mL Interval 2761.6 to 5103.8
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HAV, Heavy	3195.3 mIU/mL Interval 1603.6 to 6366.8	899.8 mIU/mL Interval 247.2 to 3274.9	3292.6 mIU/mL Interval 1603.2 to 6762.1
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HBs, None or Mild	1043.1 mIU/mL Interval 689.5 to 1578.0	534.9 mIU/mL Interval 339.9 to 841.7	230.7 mIU/mL Interval 150.5 to 353.6
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HBs, Moderate	1136.7 mIU/mL Interval 598.6 to 2158.5	467.3 mIU/mL Interval 240.5 to 908.1	132.7 mIU/mL Interval 72.6 to 242.4
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption Anti-HBs, Heavy	3246.9 mIU/mL Interval 1161.2 to 9078.8	223.4 mIU/mL Interval 91.7 to 544.2	96.6 mIU/mL Interval 27.3 to 341.8

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=165 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=169 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=162 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Concomitant Medication Anti-HAV, concomitant medication	2680.3 mIU/mL Interval 2187.8 to 3283.7	1398.4 mIU/mL Interval 1150.1 to 1700.2	3752.7 mIU/mL Interval 3097.9 to 4546.0
Anti-HAV and Anti-HBs Antibody Concentrations, by Concomitant Medication Anti-HAV, no concomitant medication	3505.5 mIU/mL Interval 1541.7 to 7971.1	1343.0 mIU/mL Interval 801.0 to 2251.9	3225.1 mIU/mL Interval 1470.3 to 7074.1
Anti-HAV and Anti-HBs Antibody Concentrations, by Concomitant Medication Anti-HBs, concomitant medication	1138.0 mIU/mL Interval 804.2 to 1610.3	533.4 mIU/mL Interval 368.9 to 771.4	174.1 mIU/mL Interval 124.6 to 243.3
Anti-HAV and Anti-HBs Antibody Concentrations, by Concomitant Medication Anti-HBs, no concomitant medication	1329.9 mIU/mL Interval 405.9 to 4356.9	170.8 mIU/mL Interval 30.3 to 962.4	255.8 mIU/mL Interval 36.3 to 1803.6

SECONDARY outcome

Timeframe: At Month 7

Outcome measures

Outcome measures
Measure	Twinrix Group n=181 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=182 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HAV,no medical condition	4765.5 mIU/mL Interval 3301.7 to 6878.3	2187.5 mIU/mL Interval 1387.0 to 3450.0	5531.9 mIU/mL Interval 3806.7 to 8038.7
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HAV,past medical condition	3438.3 mIU/mL Interval 1944.8 to 6078.7	1882.2 mIU/mL Interval 1275.1 to 2778.2	4073.9 mIU/mL Interval 1915.1 to 8666.5
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HAV,current medical condition	2445.3 mIU/mL Interval 1935.9 to 3088.8	1245.2 mIU/mL Interval 997.2 to 1554.8	3464.3 mIU/mL Interval 2800.4 to 4285.7
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HBs,no medical condition	2743.4 mIU/mL Interval 1191.4 to 6316.9	435.2 mIU/mL Interval 146.1 to 1296.7	345.1 mIU/mL Interval 104.8 to 1136.5
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HBs,past medical condition	1537.3 mIU/mL Interval 316.0 to 7478.8	799.5 mIU/mL Interval 292.4 to 2186.4	349.4 mIU/mL Interval 117.6 to 1038.0
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition Anti-HBs,current medical condition	964.6 mIU/mL Interval 668.1 to 1392.8	464.4 mIU/mL Interval 304.0 to 709.5	152.2 mIU/mL Interval 105.3 to 220.0

SECONDARY outcome

Timeframe: At Month 12 (M12), Month 24 (M24) and Month 36 (M36)

Population: The analysis was performed Long Term According-To-Protocol (LT ATP) cohort for immunogenicity, which included all subjects who were included in the ATP cohort for immunogenicity in the primary study and who came within the blood sampling time interval at Months 12, 24 and 36.

Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).

Outcome measures

Outcome measures
Measure	Twinrix Group n=171 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=167 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HAV, M12	162 Participants	165 Participants	164 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HAV, M24	164 Participants	170 Participants	163 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HAV, M36	158 Participants	159 Participants	148 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HBs, M12 AUSAB	153 Participants	134 Participants	109 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HBs, M24 AUSAB	136 Participants	123 Participants	74 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HBs, M24 in-house	137 Participants	129 Participants	76 Participants
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value Anti-HBs, M36 in-house	124 Participants	105 Participants	67 Participants

SECONDARY outcome

Timeframe: At Month 12 (M12), Month 24 (M24) and Month 36 (M36)

Population: The analysis was performed on the LT ATP cohort for immunogenicity, which included all subjects who were included in the ATP cohort for immunogenicity in the primary study and who came within the blood sampling time interval at Months 12, 24 and 36.

A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).

Outcome measures

Outcome measures
Measure	Twinrix Group n=171 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=167 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen Anti-HBs, M12 AUSAB	147 Participants	124 Participants	93 Participants
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen Anti-HBs, M24 AUSAB	127 Participants	88 Participants	50 Participants
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen Anti-HBs, M24 in-house	125 Participants	99 Participants	56 Participants
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen Anti-HBs, M36 in-house	104 Participants	75 Participants	45 Participants

SECONDARY outcome

Timeframe: At Month 12 (M12), Month 24 (M24) and Month 36 (M36)

Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).

Outcome measures

Outcome measures
Measure	Twinrix Group n=171 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=176 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=167 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HAV, M12	891.0 mIU/mL Interval 747.3 to 1062.2	530.6 mIU/mL Interval 442.0 to 637.1	1200.5 mIU/mL Interval 999.3 to 1442.1
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HAV, M24	271.6 mIU/mL Interval 229.0 to 322.2	209.9 mIU/mL Interval 176.3 to 249.8	362.0 mIU/mL Interval 303.5 to 431.8
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HAV, M36	216.9 mIU/mL Interval 182.6 to 257.6	185.4 mIU/mL Interval 155.7 to 220.7	278.5 mIU/mL Interval 229.4 to 338.2
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HBs, M12 AUSAB	339.2 mIU/mL Interval 248.6 to 462.9	149.4 mIU/mL Interval 106.4 to 209.7	53.1 mIU/mL Interval 39.3 to 71.6
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HBs, M24 AUSAB	113.2 mIU/mL Interval 83.9 to 152.8	46.5 mIU/mL Interval 33.0 to 65.4	21.3 mIU/mL Interval 15.5 to 29.4
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HBs, M24 in-house	99.3 mIU/mL Interval 75.4 to 130.7	40.8 mIU/mL Interval 30.4 to 54.9	22.3 mIU/mL Interval 16.9 to 29.4
Anti-HAV and Anti-HBs Antibody Concentrations Anti-HBs, M36 in-house	72.1 mIU/mL Interval 53.1 to 98.0	34.1 mIU/mL Interval 24.6 to 47.2	18.9 mIU/mL Interval 14.1 to 25.3

SECONDARY outcome

Timeframe: From Day 0 up to Month 7

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: 3 subjects reported SAEs prior to administration of the first dose of vaccination.

Outcome measures

Outcome measures
Measure	Twinrix Group n=199 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=200 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=197 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With Serious Adverse Events (SAEs)	11 Participants	14 Participants	16 Participants

SECONDARY outcome

Timeframe: At Month 12 (M12), Month 24 (M24) and Month 36 (M36)

Population: The analysis was performed on the Long Term Total Vaccinated Cohort, which included all subjects who had received at least one dose of the study vaccine in the primary study and who returned for the current blood sample time point at one, two and three years (Month 12, 24, 36) after first vaccination.

Outcome measures

Outcome measures
Measure	Twinrix Group n=197 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=198 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=194 Participants Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Number of Subjects With SAEs Any SAE(s), M12	0 Participants	0 Participants	0 Participants
Number of Subjects With SAEs Any SAE(s), M24	0 Participants	0 Participants	0 Participants
Number of Subjects With SAEs Any SAE(s), M36	0 Participants	0 Participants	0 Participants

Adverse Events

Twinrix Group

Serious events: 11 serious events

Other events: 0 other events

Deaths: 1 deaths

Engerix-B+Havrix Group

Serious events: 14 serious events

Other events: 0 other events

Deaths: 2 deaths

HB VAX PRO+Vaqta Group

Serious events: 16 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

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

Serious adverse events
Measure	Twinrix Group n=199 participants at risk Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Engerix-B+Havrix Group n=200 participants at risk Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	HB VAX PRO+Vaqta Group n=197 participants at risk Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.
Infections and infestations Pneumonia	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	1.0% 2/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Cardiac disorders Adams-Stokes syndrome	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Blood and lymphatic system disorders Anaemia	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Cardiac disorders Angina pectoris	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Eye disorders Angle closure glaucoma	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Cardiac disorders Atrial fibrillation	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Eye disorders Blepharochalasis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Cardiac disorders Cardiac arrest	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Carotid artery stenosis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Eye disorders Cataract	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Hepatobiliary disorders Cholecystitis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Cardiac disorders Coronary artery occlusion	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Infections and infestations Cystitis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Dizziness	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Epilepsy	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Blood and lymphatic system disorders Gastroduodenal ulcer	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Eye disorders Glaucoma	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Hepatobiliary disorders Hepatic neoplasm malignant	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Gastrointestinal disorders Ileus	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Gastrointestinal disorders Inguinal hernia	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Injury, poisoning and procedural complications Lower limb fracture	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Infections and infestations Meningitis	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Myasthenia gravis	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Respiratory, thoracic and mediastinal disorders Nasal cyst	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Paraesthesia	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Infections and infestations Pyelonephritis	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.50% 1/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Renal and urinary disorders Renal colic	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Renal and urinary disorders Stress incontinence	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Nervous system disorders Subdural haematoma	0.50% 1/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/199 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.00% 0/200 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.	0.51% 1/197 • SAEs: from Day 0 up to Month 36. Only SAEs were collected during this study. Per Study Protocol, Other (non-serious) Adverse Events were not planned to be collected in this study.