Study of Efficacy and Safety, Tolerability and Pharmacoki... | NCT02058108

ID	Type	Description	Link
2012-004942-14	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Telbivudine	Experimental	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily	Drug: Telbivudine
Placebo	Placebo Comparator	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Telbivudine	Drug	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24	The primary objective of this study was to demonstrate the antiviral efficacy of telbivudine compared to placebo in pediatric patients (2- < 18 years) by determining the percentage of patients achieving serum HBV DNA level of <300 copies/mL (51 IU/mL) at Week 24.	Week 24

Secondary Outcomes

Measure	Description	Time Frame
Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104	The antiviral efficacy at Weeks 52 and 104 was to be evaluated by: a) the proportion of patients achieving HBV DNA <300 copies/mL (51 IU/mL) at Week 52 and Week 104; b) the proportion of patients achieving HBV DNA < Lower Limit of Quantification (LLOQ), <1000 copies/ml (or 200 IU/mL), <10,000 copies/ml (or 2 000 IU/mL) and ≥10,000 copies/mL (or 2 000 IU/mL) at Week 24, 52 and 104; c) the proportion of patients achieving Serum HBV DNA reduction from baseline; d) the time to achieve HBV DNA <300 copies/mL (51 IU/mL); e) the proportion of patients with Primary non-response. Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Clinical history compatible with compensated chronic hepatitis B
Documented compensated chronic hepatitis B defined by the following:
1. Positive serum HBsAg at screening and at least one other documentation of HBsAg positive at least 6 months prior to screening
2. For HBeAg positive patients at screening, significant biologic and/or histologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (serum HBV DNA level ≥ 5 log10 copies/mL (or 20 000 IU/mL) (COBAS Taqman®) at screening ; serum ALT ≥ 1.5×ULN and < 10×ULN (pediatric ULN) for two times during the screening period or within 6 months prior to screening
3. For HBeAg negative patients at screening, significant biologic and/or histologic signs of disease activity following EASL guidelines recommendations for CHB pediatric patients (serum HBV DNA level ≥ 4 log10 copies/mL (or 2 000 IU/mL) (COBAS Taqman®) at screening) ; serum ALT ≥ 1.0 ×ULN and < 10×ULN (pediatric ULN) for two times during the screening period or within 12 months prior to screening)

Key Exclusion Criteria:

Patients with acute or chronic infection of HCV, HDV, HIV, or with acute infection of HAV, HEV, CMV, EBV, or HSV.
Patient has received treatment of interferon or any other immunomodulatory agents within the last 12 months prior to screening or any nucleoside or nucleotide drugs or other anti-CHB treatment (approved or investigational) at any time before screening
Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir, systemic corticosteroids, potentially hepatotoxic drugs or nephrotoxic drugs or chemotherapy
Patient has one or more additional known primary or secondary causes of liver disease, other than CHB; has a decompensated liver disease ; is a Liver transplant recipient or organ or bone marrow transplant recipient.
History of any other acute or chronic medical condition (that in the opinion of the investigator would make the patient unsuitable for inclusion into the study.
Patient has a history of myopathy, myositis, persistent muscle weakness or persistent high serum CK levels (≥7×ULN), any muscular disease
Patient receiving any drugs potentially associated with myopathy within 3 months prior to screening
Any other clinical significant disease, condition or abnormality, unrelated to their HBV infection at screening, as assessed by the investigator

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Sofia	Sofia-Grad	1700	Bulgaria
Novartis Investigative Site

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 22, 2016	Jul 4, 2019

Arm/Group Information

ID	Title	Description
BG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
BG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00010.2± 4.88 BG0019.1± 4.89 BG00210.0± 4.86

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014 BG0014 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

Caucasian

Title	Measurements
	BG00040 BG00110 BG002

HBV DNA

Mean

Standard Deviation

log10 copies/mL

Title

Denominators

Categories

Title	Measurements
	BG0009.1± 1.14 BG0018.2± 2.26 BG002

Participants with alanine aminotransferase (ALT) - Multiples of upper limits of normal (ULN)

Serum ALT normalization is an important clinically relevant efficacy endpoint. Elevated serum ALT levels are thought to reflect underlying hepatitis disease activity (i.e. active liver inflammation). Correspondingly, ALT normalization is an accepted therapeutic goal in hepatitis studies as it is thought to reflect a substantial reduction in hepatic disease activity. Measurement at baseline.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 1 × ULN	BG0004 BG001

Participants with aspartate aminotransferase (AST) - Multiples of upper limits of normal (ULN)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 1 × ULN	BG00026 BG0015 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients Achieving Serum HBV DNA Level of <300 Copies/mL (51 IU/mL) at Week 24

The primary objective of this study was to demonstrate the antiviral efficacy of telbivudine compared to placebo in pediatric patients (2- < 18 years) by determining the percentage of patients achieving serum HBV DNA level of <300 copies/mL (51 IU/mL) at Week 24.

The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered.

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Units	Counts
Participants	OG00041 OG0018

Title

Denominators

Categories

Title	Measurements
	OG0005 OG0011

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	HBV DNA level of <300 copies/mL (51 IU/mL) at Week 24	Fisher Exact		1.0000		Mean Difference (Net)	-0.30			2-Sided	95	-37.03	36.75					Other	Missing assessment imputed using the closest available assessment	Exact confidence interval for the difference in percentage

Secondary

Number of Patients Achieving HBV DNA< 300 Copies/mL (51 IU/mL) at Week 52 and Week 104

The antiviral efficacy at Weeks 52 and 104 was to be evaluated by: a) the proportion of patients achieving HBV DNA <300 copies/mL (51 IU/mL) at Week 52 and Week 104; b) the proportion of patients achieving HBV DNA < Lower Limit of Quantification (LLOQ), <1000 copies/ml (or 200 IU/mL), <10,000 copies/ml (or 2 000 IU/mL) and ≥10,000 copies/mL (or 2 000 IU/mL) at Week 24, 52 and 104; c) the proportion of patients achieving Serum HBV DNA reduction from baseline; d) the time to achieve HBV DNA <300 copies/mL (51 IU/mL); e) the proportion of patients with Primary non-response.

Due to early termination of the study and limited number of enrolled patients on track to complete 52 weeks of participation (8 patients overall), only descriptive analysis performed at Week 52 and Week 104.

The Full Analysis Set (FAS), which consisted of all randomized patients to whom study treatment had been assigned, was considered. Only patients with efficacy data within censoring date included in the analysis.

Posted

Count of Participants

Participants

Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001

Secondary

Number of Patients Whose Baseline ALTs Were Abnormal and Subsequently Normalized at Week 24, 52 and 104

The biochemical response at Weeks 24, 52 and 104 was to be evaluated by the proportion of patients whose baseline ALTs were abnormal (defined as ALT >1 x Upper Limit of Normal [ULN]) and subsequently normalized.

Posted

Count of Participants

Participants

Week 24, Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Secondary

Number of Patients With HBeAg Loss, HBeAg Seroconversion at Week 24, 52 and 104

The serological response at Weeks 24, 52 and 104 was to be evaluated by: a) the proportion of HBeAg positive patients at baseline who subsequently have HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg with detectable HBeAb); b) the proportion of HBsAg positive patients at baseline who subsequently have HBsAg loss and HBsAg seroconversion (defined as loss of HBsAg with detectable HBsAb).

Posted

Count of Participants

Participants

Week 24, Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Secondary

Number of Patients With HBsAg Loss, HBsAg Seroconversion at Week 24, 52 and 104

Posted

Count of Participants

Participants

Week 24, Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Secondary

Number of Patients Achieving a Composite Endpoints (HBV DNA < 300 Copies/mL (51 IU/mL), ALT Normalization and HBeAg Seroconversion) at Week 52 and 104

The proportion of patients achieving composite endpoints at Week 52 and 104 was to be evaluated by the proportion of patients achieving: a) HBV DNA <300 copies/mL (51 IU/mL); b) ALT normalization and HBeAg seroconversion for HBeAg positive patients only; c) HBV DNA <300 copies/mL (51 IU/mL) and ALT normalization for HBeAg negative patients.

Posted

Count of Participants

Participants

Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo

Secondary

Number of Patients Achieving Cumulative Rate of Virological Breakthrough (VB) at Week 52 and 104

The assessment of virological breakthrough (VB) was to be evaluated by: a) the cumulative rate of patients with confirmed VB at Week 52 and Week 104; b) the time to VB.

Posted

Count of Participants

Participants

Week 52, Week 104

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Secondary

Number of Participants With Treatment Emergent Genotypic Resistance Associated With VB, or in Patients With HBV DNA≥300 Copies/mL (51 IU/mL) at Week 24 and Discontinued From the Study

Assessment of the presence of treatment emergent genotypic resistance (confirmed by genotypic sequencing) associated with virological breakthrough over the study period, or in patients with HBV DNA≥300 copies/mL (51 IU/mL) at Week 24 and discontinued from the study treatment (or at discontinuation if prior to Week 24 for subjects with at least 16 weeks of LDT treatment)

Posted

Count of Participants

Participants

Week 24

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Secondary

Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Death

Evaluation of the safety and tolerability of Telbivudine defined by AEs, SAEs, adverse events of special interest (AESI) (including muscle related events) and death; laboratory evaluations specifically on-treatment and post-treatment ALT flares, incidence and clinical significance of CK elevations; growth and development (linear growth and sexual maturation); development of liver decompensation and/or HCC.

Only descriptive analysis performed.

The Safety Set, which consisted of all patients who received at least one dose of study drug during the treatment period, was considered.

Posted

Count of Participants

Participants

From first dose of study treatment to 30 days after last dose of study treatment, up to 112 weeks

ID	Title	Description
OG000	Telbivudine	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily
OG001	Placebo	Patients of any age and weight < 30kg: placebo oral solution corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight ≥ 30kg: placebo oral solution corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: placebo tablet, corresponding to 1 tablet p.o. once daily. Placebo randomized patients were offered optional telbivudine administration at week 24.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Initial LdT (Telbivudine)	Patients of any age and weight< 30kg: telbivudine oral solution (20 mg/mL): 20 mg/kg up to 600 mg q.d corresponding to weight (kg) x1mL, p.o. once daily Patients < 12 years old and weight≥ 30kg: telbivudine oral solution (20mg/mL), 600 mg/day corresponding to 30 mL p.o. once daily Patients ≥ 12 years old and weight ≥ 30kg: telbivudine film-coated tablet, 600 mg/day, corresponding to 1 tablet p.o. once daily	43	43	20	43
EG001	Initial Placebo on Placebo Treatment	Initial Placebo patients who did not switched to LdT treatment	10	10	4	10
EG002	Initial Placebo on LdT Treatment After Switching	Initial Placebo patients who switched to LdT treatment	5	5	1	5
EG003	All Ldt	Initial LdT and Initial Placebo on LdT treatment after switching combined	48	48	21	48

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ear pain	Ear and labyrinth disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG0030 affected48 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Exanthema subitum	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Laryngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected43 at risk EG0010 affected10 at risk EG0021 affected5 at risk EG003
Otitis media	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Tonsillitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG003
Varicella	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Viral infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0003 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected43 at risk EG0010 affected10 at risk EG0020 affected5 at risk EG003
Antibiotic prophylaxis	Surgical and medical procedures	MedDRA (19.1)	Systematic Assessment	EG0000 affected43 at risk EG0011 affected10 at risk EG0020 affected5 at risk EG003

ID	Term
D006509	Hepatitis B
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013936	Thymidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides