An Extension Study of HGT-HIT-045 Evaluating Long-Term Sa... | NCT01506141

ID	Type	Description	Link
2011-000212-25	EudraCT Number

Label	Type	Description	Intervention Names
Idursulfase-IT 1 milligram (mg)	Experimental	Participants will receive 1 mg idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and standard-of-care (SoC) therapy of Elaprase intravenous (IV) infusions.	Drug: Idursulfase-IT Drug: Elaprase
Idursulfase-IT 10 mg	Experimental	Participants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.	Drug: Idursulfase-IT Drug: Elaprase
Idursulfase-IT 30 mg	Experimental	Participants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions.	Drug: Idursulfase-IT Drug: Elaprase

Name	Type	Description	Arm Group Labels	Other Names
Idursulfase-IT	Drug	Idursulfase-IT once monthly via IDDD.	Idursulfase-IT 1 milligram (mg) Idursulfase-IT 10 mg Idursulfase-IT 30 mg

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of a clinical trial, and whether or not considered study drug-related. TEAEs were defined as all AEs occurring on or after the first IDDD surgery date or first dose (whichever is earlier) for the participant (whether it is in this extension study or in HGT HIT-045 [NCT00920647]) and before the end of the study (EOS) visit (+30 days). For Idursulfase-IT 1 mg+10 mg arm the summary presented includes only the TEAEs that occurred while the participants were assigned to 10 mg.	From start of study drug administration up to follow-up (up to 165 months)
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters	Number of participants with clinically significant changes in laboratory parameters (chemistry, hematology, urinalysis and CSF values) were collected.	From start of study drug administration up to follow-up (up to 165 months)
Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings	Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected.	From start of study drug administration up to follow-up (up to 165 months)
CSF Chemistries: Change From Baseline in CSF Total Cell Count		Baseline, Month 163
CSF Chemistries: Change From Baseline in CSF Glucose		Baseline, Month 163

Measure	Description	Time Frame
Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase	Area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration (AUC0-infinity) of idursulfase was assessed. Participants in 1 mg arm group were assessed for Pharmacokinetic (PK) analysis in the HGT-HIT-045 study.

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ann & Robert H Lurie Childrens Hospital of Chicago		Chicago	Illinois	60611	United States
University of North Carolina at Chapel Hill

PubMed Identifier	Type	Citation	Retractions
17185020	Background	Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
16912578	Background	Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb.

Label	URL
To obtain more information on the study, click here/on this link	View source

ID	Title	Description
FG000	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 17, 2021	Apr 28, 2025

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 Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of a clinical trial, and whether or not considered study drug-related. TEAEs were defined as all AEs occurring on or after the first IDDD surgery date or first dose (whichever is earlier) for the participant (whether it is in this extension study or in HGT HIT-045 [NCT00920647]) and before the end of the study (EOS) visit (+30 days). For Idursulfase-IT 1 mg+10 mg arm the summary presented includes only the TEAEs that occurred while the participants were assigned to 10 mg.

Posted

Count of Participants

Participants

From start of study drug administration up to follow-up (up to 165 months)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Units	Counts
Participants	OG0004 OG00110 OG0025

Title

Denominators

Categories

Title	Measurements
	OG0004 OG00110 OG0025

Primary

Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in Laboratory Parameters

Number of participants with clinically significant changes in laboratory parameters (chemistry, hematology, urinalysis and CSF values) were collected.

Posted

Count of Participants

Participants

From start of study drug administration up to follow-up (up to 165 months)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg

Primary

Number of Participants With Clinically Significant Changes or Apparent Difference Across Treatment Groups in 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected.

Posted

Count of Participants

Participants

From start of study drug administration up to follow-up (up to 165 months)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Primary

CSF Chemistries: Change From Baseline in CSF Total Cell Count

Safety Population included all eligible participants from HGT-HIT-045 who had agreed to participate in the extension study and had either surgical implantation of an IDDD or intrathecal administration of study drug in the extension study. Overall number analyzed are the number of participants who had data at Baseline. Number analyzed indicates the number of participants with data available for analyses at specified time points.

Posted

Mean

Standard Deviation

10^6 cells/Liter (L)

Baseline, Month 163

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Primary

CSF Chemistries: Change From Baseline in CSF Glucose

Posted

Mean

Standard Deviation

millimoles per liter (mmol/L)

Baseline, Month 163

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Primary

CSF Chemistries: Change From Baseline in CSF Protein

Posted

Mean

Standard Deviation

grams per liter (g/L)

Baseline, Month 163

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Primary

Number of Participants With Anti-idursulfase Antibodies in CSF

Posted

Count of Participants

Participants

From start of study drug administration up to follow-up (up to 165 months)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Primary

Number of Participants With Anti-idursulfase Antibodies in Serum

Posted

Count of Participants

Participants

From start of study drug administration up to follow-up (up to 165 months)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.

Secondary

Area Under the Curve Extrapolated to Infinity (AUC0-infinity) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration (AUC0-infinity) of idursulfase was assessed. Participants in 1 mg arm group were assessed for Pharmacokinetic (PK) analysis in the HGT-HIT-045 study.

PK population included all participants who received study drug & participated in the scheduled pharmacokinetic studies,& for whom at least 1 post-dose PK blood sample was collected. Overall number analyzed indicates number of participants with data available for analyses. Number analyzed indicates number of participants with data available for analyses at specified time points.

Posted

Mean

Standard Deviation

hours*nanograms per milliliter(h*ng/mL)

15 minutes prior to IT injection, at 1,2,3,4,6,8,12,24,30,36 hours (±1 hour) following IT injection on Day 2 of Weeks 3,23, for 1 mg arm group and on Day 2 of Weeks 3,23, Months 19,31,43,55,67,79 for 10 and 30 mg arm groups

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Area Under the Curve From the Time of Dosing to the Last Measureable Concentration (AUC0-t) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

PK population included all participants who received study drug and participated in the scheduled pharmacokinetic studies, and for whom at least 1 post-dose PK blood sample was collected. Overall number analyzed indicates the number of participants with data available for analyses. Number analyzed indicates the number of participants with data available for analyses at specified time points.

Posted

Mean

Standard Deviation

h*ng/mL

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Maximum Observed Concentration (Cmax) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Time of Maximum Observed Concentration (Tmax) of Idursulfase Administered in as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Total Body Clearance for Extravascular Administration Divided by the Fraction of Dose Absorbed (Cl/F) of Idursulfase-IT Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

Posted

Mean

Standard Deviation

liters per hour (L/h)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration Divided by the Fraction of Dose Absorbed (Vz/F) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

Posted

Mean

Standard Deviation

liters

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

First Order Rate Constant (Lambda z) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study.

Posted

Mean

Standard Deviation

per hour (/h)

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Terminal Half-life (t1/2) of Idursulfase Administered as Intrathecal and in Conjunction With Elaprase

Participants in 1 mg arm group were assessed for PK analysis in the HGT-HIT-045 study. T1/2 is calculated by dividing 0.693 by Lambda z. Here, 0.693 is the natural logarithm of 2 and Lambda z is the first order rate constant.

Posted

Median

Full Range

hours

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.

Secondary

Total Body Clearance (CL) of Elaprase

Participants who received only Elaprase in HGT-HIT-045 and had evaluable samples were analyzed for this outcome measure. Number analyzed indicates the number of participants with data available for analyses at the specified time point.

Posted

Mean

Standard Deviation

liters per hour (L/h)

15 minutes prior to IV infusion, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 9, 11, and 24 hours during/after the IV infusion on Days 3-7 of Weeks 3 and 23

ID	Title	Description
OG000	Elaprase IV Infusion 0.5 mg/kg	Participants received 0.5 mg/kg SoC therapy of Elaprase IV infusions for up to a maximum of 157.2 months.

Units	Counts
Participants	OG000

Secondary

Observed Steady-state Volume of Distribution (Vss) of Elaprase

Posted

Mean

Standard Deviation

liters

15 minutes prior to IV infusion and at multiple timepoint (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23

ID	Title	Description
OG000	Elaprase IV Infusion 0.5 mg/kg	Participants received 0.5 mg/kg SoC therapy of Elaprase IV infusions for up to a maximum of 157.2 months.

Units	Counts
Participants	OG000

Secondary

Volume of Distribution (Vz) of Elaprase

Volume of distribution associated with the terminal slope (Vz) of Elaprase was assessed.

Posted

Mean

Standard Deviation

liters

15 minutes prior to IV infusion and at multiple timepoints (0.5, 1, 1.5, 2, 2.5, and 3 hours during the infusion; and at 3.5, 4, 5, 6, 7, 9, 11, and 24 hours) following IV infusion on Days 3-7 of Weeks 3 and 23

ID	Title	Description
OG000	Elaprase IV Infusion 0.5 mg/kg	Participants received 0.5 mg/kg SoC therapy of Elaprase IV infusions for up to a maximum of 157.2 months.

Units	Counts
Participants	OG000

Secondary

Mean Residence Time Extrapolated to Infinity (MRT0-inf) of Elaprase

Posted

Mean

Standard Deviation

hours

ID	Title	Description
OG000	Elaprase IV Infusion 0.5 mg/kg	Participants received 0.5 mg/kg SoC therapy of Elaprase IV infusions for up to a maximum of 157.2 months.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in CSF Biomarkers

Change from baseline in CSF biomarkers glycosaminoglycan (GAG [heparan sulfate (HS)/dermatan sulfate (DS)]) was assessed.

Safety Population included all eligible participants from HGT-HIT-045 who had agreed to participate in the extension study and have had either surgical implantation of an IDDD or intrathecal administration of study drug in the extension study. Number analyzed is the number of participants with data available for analyses. A few participants from the 1 mg arm had transitioned to 10 mg arm before the analysis at Month 7 was performed for this outcome measure.

Posted

Mean

Standard Deviation

ng/mL

Baseline, Months 7, 55, and 139

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002

Secondary

Change From Baseline in Urinary Glycosaminoglycan (GAG)

mg GAG/mmol creatinine stands for milligrams of GAG per millimole of creatinine.

Posted

Mean

Standard Deviation

mg GAG/mmol creatinine

Baseline, Months 7, 55, and 163

ID	Title	Description
OG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
OG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.
OG002	Idursulfase-IT 30 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Abnormal behaviour	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Accidental exposure to product	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Adenoidal hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Adenovirus infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Affect lability	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Aggression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0013 affected10 at risk EG0023 affected5 at risk
Agitation	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0018 affected10 at risk EG0023 affected5 at risk
Agitation postoperative	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0020 affected5 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
Angiokeratoma	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Anisocytosis	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Anorectal infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Anticipatory anxiety	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Antisocial behaviour	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Anxiety	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Aortic valve disease	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Application site erythema	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Aptyalism	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0022 affected5 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0023 affected5 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Asthenia	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Atrioventricular block first degree	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Avulsion fracture	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0023 affected5 at risk
Bacteraemia	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bacterial disease carrier	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bacterial test	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Bacterial test positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bacterial tracheitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Band neutrophil count increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Base excess decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bilirubin conjugated increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bite	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Blood albumin decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Blood bicarbonate decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Blood bilirubin increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Blood calcium decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Blood chloride increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Blood lactic acid increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Blood phosphorus decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Blood phosphorus increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Blood pressure decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0017 affected10 at risk EG0022 affected5 at risk
Blood pressure diastolic decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0018 affected10 at risk EG0022 affected5 at risk
Blood pressure diastolic increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0018 affected10 at risk EG0022 affected5 at risk
Blood pressure fluctuation	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Blood pressure increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0016 affected10 at risk EG0021 affected5 at risk
Blood pressure systolic decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0017 affected10 at risk EG0022 affected5 at risk
Blood pressure systolic increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0018 affected10 at risk EG0022 affected5 at risk
Blood sodium increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Blood thyroid stimulating hormone decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Blood triglycerides increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Blood urea increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Bloody discharge	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Body temperature decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0016 affected10 at risk EG0022 affected5 at risk
Body temperature increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Bone density decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bradycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Breath sounds abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Bronchitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Bronchomalacia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Bruxism	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Burns first degree	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Burns second degree	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
C-reactive protein increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
CSF cell count increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0017 affected10 at risk EG0021 affected5 at risk
CSF culture positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
CSF glucose decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
CSF lymphocyte count increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
CSF neutrophil count positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
CSF protein decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
CSF protein increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0017 affected10 at risk EG0023 affected5 at risk
CSF white blood cell count increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Candida nappy rash	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Carbon dioxide decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Cardiac murmur	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0024 affected5 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0023 affected5 at risk
Catheter site bruise	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Catheter site erythema	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Cerebral atrophy	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Cerebral ventricle dilatation	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0016 affected10 at risk EG0021 affected5 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Chapped lips	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Chills	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Choking	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Clonus	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0023 affected5 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Colitis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Congenital bowing of long bones	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Conjunctivitis	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0021 affected5 at risk
Conjunctivitis bacterial	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Constipation	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0017 affected10 at risk EG0021 affected5 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0018 affected10 at risk EG0023 affected5 at risk
Convulsion	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0016 affected10 at risk EG0021 affected5 at risk
Coordination abnormal	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Corona virus infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Coronavirus test positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0018 affected10 at risk EG0023 affected5 at risk
Crepitations	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Croup infectious	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Crystal urine present	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Cyanosis	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Cyst	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dandruff	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Deafness bilateral	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Deafness unilateral	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Decreased activity	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0015 affected10 at risk EG0021 affected5 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dental caries	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0016 affected10 at risk EG0021 affected5 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Depressed mood	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Depression	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Device breakage	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Device connection issue	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Device dislocation	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Device malfunction	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0021 affected5 at risk
Device occlusion	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0018 affected10 at risk EG0023 affected5 at risk
Discomfort	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Drooling	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Dry eye	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Dyskinesia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dysmorphism	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Dysphemia	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0021 affected5 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Ear disorder	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Ear infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0017 affected10 at risk EG0022 affected5 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Eating disorder	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eczema eyelids	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Electroencephalogram abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Energy increased	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Enterobiasis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Enterovirus infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Enuresis	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Epilepsy	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Eructation	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0023 affected5 at risk
Excessive granulation tissue	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0017 affected10 at risk EG0024 affected5 at risk
Exposure via ingestion	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Extravasation	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Eye discharge	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eye infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Eye injury	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eye irritation	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eye swelling	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Eyelid infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Eyelid margin crusting	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Eyelid oedema	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Face oedema	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0016 affected10 at risk EG0024 affected5 at risk
Fatigue	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Flatulence	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Flushing	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0022 affected5 at risk
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Foreign body	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Fungal infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Fungal skin infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Furuncle	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gait disturbance	General disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0016 affected10 at risk EG0023 affected5 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Gastritis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gastroenteritis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Generalised oedema	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Glaucoma	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Haematocrit decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Haematoma	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Haemoglobin decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Headache	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
Heart rate decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0018 affected10 at risk EG0022 affected5 at risk
Heart rate increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0021 affected5 at risk
Heart rate irregular	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Heart sounds abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Herpes simplex	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Herpes zoster	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Hordeolum	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Human bite	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hyperreflexia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Hypersomnia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Hypertension	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0022 affected5 at risk
Hypertonia	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hypochromasia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hypotension	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0023 affected5 at risk
Hypothermia	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Ileus	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Impetigo	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Implant site effusion	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Implant site erythema	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Implant site infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Implant site pain	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Implant site rash	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Implant site reaction	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Implant site scar	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Implant site swelling	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0021 affected5 at risk
Impulsive behaviour	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Incision site erythema	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Influenza	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Influenza like illness	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Infusion site bruising	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Infusion site extravasation	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0023 affected5 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Insomnia	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0023 affected5 at risk
Intertrigo	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0022 affected5 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0023 affected5 at risk
Iron binding capacity total decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Irritability	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Joint contracture	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Knee deformity	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Kyphosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Labyrinthitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Lacrimation increased	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Laryngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Laryngospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Left atrial dilatation	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Left atrial hypertrophy	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lethargy	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Leukocyte vacuolisation	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lice infestation	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Limb crushing injury	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lip dry	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Lip swelling	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Local swelling	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Localised infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Loose tooth	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Lymphocyte count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Lymphocyte morphology abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Macrogenia	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Malaise	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0022 affected5 at risk
Mastication disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mastoid disorder	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mastoid effusion	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mastoiditis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mean cell haemoglobin concentration decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mean cell haemoglobin decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mean cell volume abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mean cell volume decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Medical device complication	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Microcytosis	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Middle ear effusion	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Middle ear inflammation	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Miliaria	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Mitral valve stenosis	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Monocyte count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Monocyte morphology abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Mood altered	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mood swings	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Motion sickness	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Movement disorder	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Mucous stools	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Muscle spasticity	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nail infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0015 affected10 at risk EG0023 affected5 at risk
Nasal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nasal odour	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nasal turbinate hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nasogastric output abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0018 affected10 at risk EG0021 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Negativism	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nerve compression	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Neutrophil count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Nitrite urine present	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Nuclear magnetic resonance imaging abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Nuclear magnetic resonance imaging brain abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Ocular hyperaemia	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Oedema peripheral	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Onychomycosis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Oral herpes	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Osteomyelitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Otitis externa	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Otitis media	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0015 affected10 at risk EG0022 affected5 at risk
Otitis media acute	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Otitis media chronic	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Otorrhoea	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0015 affected10 at risk EG0022 affected5 at risk
Oxygen saturation decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0017 affected10 at risk EG0022 affected5 at risk
PCO2 decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pain	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0023 affected5 at risk
Pallor	Vascular disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Papilloedema	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Parkinsonian gait	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Paronychia	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Penile erythema	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Periorbital haematoma	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Personality change	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pharyngeal disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Pharyngitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Pica	Metabolism and nutrition disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Pityriasis rosea	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Platelet count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Pneumonia	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0020 affected5 at risk
Pneumonia viral	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Post procedural discomfort	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Post procedural swelling	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Posture abnormal	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Presyncope	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Procedural complication	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Procedural headache	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Procedural hypotension	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0004 affected4 at risk EG0018 affected10 at risk EG0025 affected5 at risk
Procedural site reaction	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Procedural vomiting	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Protein total decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0022 affected5 at risk
Protein total increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Protein urine	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Protein urine present	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Proteinuria	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Protrusion tongue	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Pruritus allergic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Pseudomonas test positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Psychomotor hyperactivity	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Punctate basophilia	Blood and lymphatic system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Puncture site pain	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pupils unequal	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pyramidal tract syndrome	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Pyrexia	General disorders	MedDRA 16.1	Systematic Assessment	EG0003 affected4 at risk EG0019 affected10 at risk EG0025 affected5 at risk
Radiculopathy	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0017 affected10 at risk EG0020 affected5 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Red blood cell burr cells present	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Red blood cell count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Red blood cell count increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Red blood cells CSF positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Red blood cells urine	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Red blood cells urine positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Red cell distribution width increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Red man syndrome	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Regressive behaviour	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Respiration abnormal	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Respiratory rate decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Respiratory rate increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Restlessness	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0015 affected10 at risk EG0020 affected5 at risk
Retching	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Retinal deposits	Eye disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Rhinalgia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Rhinitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0023 affected5 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0016 affected10 at risk EG0023 affected5 at risk
Rhinovirus infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Rhonchi	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Right ventricular hypertrophy	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Scab	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Scar	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Scarlet fever	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Scoliosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0023 affected5 at risk
Seasonal allergy	Immune system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Sinusitis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0021 affected5 at risk
Skin candida	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Skin infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Skull malformation	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Sleep disorder	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0021 affected5 at risk
Sleep study abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Snoring	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Social avoidant behaviour	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Somnolence	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Speech disorder	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Spinal cord neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Spinal disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Splinter	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Staring	Psychiatric disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Streptococcus test positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Suture related complication	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0023 affected5 at risk
Swollen tongue	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Syncope	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tachycardia	Cardiac disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Temporomandibular joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tendon disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Testicular swelling	Reproductive system and breast disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Thalassaemia beta	Congenital, familial and genetic disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Thirst	General disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Thyroid function test abnormal	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Thyroxine decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Thyroxine increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Tinea pedis	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0022 affected5 at risk
Toe walking	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0015 affected10 at risk EG0021 affected5 at risk
Tooth abscess	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Tooth crowding	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tooth extraction	Surgical and medical procedures	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Tooth loss	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Tooth socket haemorrhage	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Toothache	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0022 affected5 at risk
Torticollis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tracheal disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Tracheal haemorrhage	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tracheomalacia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Transaminases increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Transferrin decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Transferrin saturation increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Traumatic lumbar puncture	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Tremor	Nervous system disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tympanic membrane disorder	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0021 affected5 at risk
Tympanic membrane hyperaemia	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Tympanic membrane perforation	Ear and labyrinth disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0021 affected5 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0013 affected10 at risk EG0020 affected5 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0003 affected4 at risk EG0018 affected10 at risk EG0024 affected5 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0010 affected10 at risk EG0020 affected5 at risk
Urinary retention	Renal and urinary disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Urinary tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Urine output decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Urobilinogen urine increased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0012 affected10 at risk EG0020 affected5 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Vascular complication associated with device	General disorders	MedDRA 16.1	Systematic Assessment	EG0001 affected4 at risk EG0017 affected10 at risk EG0025 affected5 at risk
Vertebral foraminal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0022 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.1	Systematic Assessment	EG0002 affected4 at risk EG00110 affected10 at risk EG0024 affected5 at risk
Weight decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0014 affected10 at risk EG0022 affected5 at risk
White blood cell count decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
White blood cells urine positive	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk
Wound secretion	Injury, poisoning and procedural complications	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0010 affected10 at risk EG0021 affected5 at risk
Xanthochromia	Investigations	MedDRA 16.1	Systematic Assessment	EG0000 affected4 at risk EG0011 affected10 at risk EG0020 affected5 at risk

ID	Term
D016532	Mucopolysaccharidosis II
D013398	Sudden Infant Death
D016464	Lysosomal Storage Diseases

ID	Term
D038901	X-Linked Intellectual Disability
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D020271	Heredodegenerative Disorders, Nervous System
D009083	Mucopolysaccharidoses
D002239	Carbohydrate Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D017520	Mucinoses
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D003645	Death, Sudden
D003643	Death
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D066088	Infant Death

ID	Title	Description
BG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.
BG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 157.2 months.
BG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Idursulfase-IT 1 mg	Participants received 1 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 10.1 months.	4	3	4	4	4
EG001	Idursulfase-IT 10 mg	Participants received 10 mg idursulfase-IT initially intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions up to a maximum of 157.2 months. This included participants who received 1 mg idursulfase-IT initially and then switched to receive 10 mg idursulfase-IT in this arm group after Month 7 or later. These participants were analyzed in this arm group since transition to this group.	10	9	10	10	10
EG002	Idursulfase-IT 30 mg	Participants received 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions for up to a maximum of 148.2 months.	5	4	5	5	5