CONSISTENT 1: Metabolic and Safety Outcomes of Hylenex Re... | NCT01848990

Label	Type	Description	Intervention Names
Commercial Hylenex Recombinant (Formulation 1)	Experimental	Hylenex Formulation 1: For 6 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).	Drug: Commercial Hylenex® recombinant (hyaluronidase human injection) Drug: Insulin lispro Drug: Insulin aspart Drug: Insulin glulisine
Precommercial Hylenex Recombinant (Formulation 2)	Experimental	Hylenex Formulation 2: For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).	Drug: Precommercial Hylenex recombinant (hyaluronidase human injection) Drug: Insulin lispro Drug: Insulin aspart Drug: Insulin glulisine
Standard Rapid-Acting Insulin CSII	Active Comparator	Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.	Drug: Insulin lispro Drug: Insulin aspart Drug: Insulin glulisine

Name	Type	Description	Arm Group Labels	Other Names
Commercial Hylenex® recombinant (hyaluronidase human injection)	Drug		Commercial Hylenex Recombinant (Formulation 1)	Formulation 1

Measure	Description	Time Frame
Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; 6 Months
Change From Baseline to 12 Months in HbA1c	Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; 12 Months

Measure	Description	Time Frame
Rates of Hypoglycemia Events (HE) to Month 6	Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were based on measurements after 1 month up to 6 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Name	Affiliation	Role
Douglas Muchmore, MD	Halozyme Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time		Concord	California	94520	United States

Label	URL
Related Info	View source

ID	Title	Description
FG000	Commercial Hylenex Recombinant (Formulation 1)	Hylenex Formulation 1: For 12 months, participants received their regular treatment of rapid-acting continuous subcutaneous insulin infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 units (U) through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).

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

Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Participants who received at least one dose of study drug and had evaluable HbA1c data. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Posted

Mean

Standard Deviation

percentage of HbA1c

Baseline; 6 Months

ID	Title	Description
OG000	Hylenex Recombinant	For 6 months, participants received their regular treatment of rapid-acting Continuous Subcutaneous Insulin Infusion (CSII) (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.

Units	Counts
Participants	OG000296 OG001103

Title

Denominators

Categories

Title	Measurements
	OG000-0.14± 0.521 OG001-0.18± 0.687

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Sample size calculated based on approximately 400 participants (Pt) being enrolled. No more than 10% dropout rate at 6 months allowed at least 270 Hylenex and 90 standard CSII Pt to reach primary metabolic endpoint evaluation. Assuming HbA1c standard deviation of 0.7% and population difference of 0% between treatments, Pt reaching primary efficacy endpoint would provide >90% power to demonstrate HbA1c noninferiority at margin of 0.4% using confidence bound from 2-tailed 95% confidence interval.	ANOVA	Analysis of variance (ANOVA) with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect	0.4516		least squares mean treatment difference	0.05			2-Sided	95	-0.08	0.18			Hylenex minus Standard CSII

Primary

Change From Baseline to 12 Months in HbA1c

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Intent-to-Treat (ITT) Population: all randomized participants (par.). Comparisons were made by pooling all rHuPH20 pretreatment par. (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis. Only par. with available data were analyzed.

Posted

Mean

Standard Deviation

percentage of HbA1c

Baseline; 12 Months

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Rates of Hypoglycemia Events (HE) to Month 6

Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were based on measurements after 1 month up to 6 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Primary Self-Monitoring of Blood Glucose (SMBG) Analysis Population: all randomized participants who received study treatment and had SMBG data up to Month 6. Only participants with available data were analyzed. The "Number Analyzed" reflects the number of participants with at least one event.

Posted

Number

events per participant per month

After Month 1 up to Month 6

ID	Title	Description
OG000	Hylenex Recombinant	For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).

Secondary

Rates of HEs to Month 12

Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter [mg/dL] and <56 mg/dL) were based on measurements after 1 month up to 12 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

ITT Population. Only participants with available data were analyzed. The "Number Analyzed" reflects the number of participants with at least one event.

Posted

Number

events per participant per month

After Month 1 up to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001

Secondary

Rates of Hyperglycemia Events to Month 6

Overall rates of hyperglycemia (defined as blood glucose >240 mg/dL and >300 mg/dL) were based on measurements after 1 month up to 6 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Primary SMBG Analysis Population. Only participants with available data were analyzed. The "Number Analyzed" reflects the number of participants with at least one event.

Posted

Number

events per participant per month

After Month 1 up to Month 6

ID	Title	Description
OG000	Hylenex Recombinant	For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.

Secondary

Rates of Hyperglycemia Events to Month 12

Overall rates of hyperglycemia (defined as blood glucose >240 mg/dL and >300 mg/dL) were based on measurements after 1 month up to 12 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

ITT Population. Only participants with available data were analyzed. The "Number Analyzed" reflects the number of participants with at least one event.

Posted

Number

events per participant per month

After Month 1 up to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Mean Glucose Excursions at 6 Months

A 4-hour postprandial glucose excursion was measured for 3 meals after 1 month up to 6 months. For each of the 3 meals, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal (for measurements taken within 15 minutes before a meal). The average of all excursions is presented. Least Squares (LS) means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Primary SMBG Analysis Population. Only participants with available data were analyzed.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

After Month 1 up to Month 6

ID	Title	Description
OG000	Hylenex Recombinant	For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII

Secondary

Mean Glucose Excursions at 12 Months

A 4-hour postprandial glucose excursion was measured for 3 meals after 1 month up to 12 months. For each of the 3 meals, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal (for measurements taken within 15 minutes before a meal). The average of all excursions is presented. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

ITT Population. Only participants with available data were analyzed.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

After Month 1 up to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months

Standard deviation of self-monitoring blood glucose values was calculated based on measurements taken within 15 minutes before a meal, 1 month and up to 6 months after study drug administration. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Primary SMBG Analysis Population. Only participants with available data were analyzed.

Posted

Least Squares Mean

Standard Error

mg/dL

After Month 1 up to Month 6

ID	Title	Description
OG000	Hylenex Recombinant	For 6 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 6-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.

Secondary

Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months

Standard deviation of self-monitoring blood glucose values was calculated based on measurements taken within 15 minutes before a meal, 1 month and up to 12 months after study drug administration. LS means were calculated from ANOVA with treatment (Hylenex, standard rapid-acting insulin CSII) as a fixed effect. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

ITT Population. Only participants with available data were analyzed.

Posted

Least Squares Mean

Standard Error

mg/dL

After Month 1 up to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12

The number of participants achieving HbA1c goals of <7% and ≤6.5% was calculated.

ITT Population. Only participants with available data were analyzed. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Posted

Count of Participants

Participants

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Change From Baseline in Body Weight to Month 12

Baseline is defined as the last measurement prior to randomization.

Posted

Mean

Standard Deviation

kilograms

Baseline; Week 2; Months 1, 2, 3, 4, 6, 9, and 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Average of Daily Insulin Doses (Bolus, Basal, and Total)

The daily bolus insulin dose is calculated as the daily prandial (occurring before a meal) insulin dose plus the daily corrective insulin dose. Cumulative basal dosage is to generally be within 40% to 60% of the total daily dose.

Posted

Least Squares Mean

Standard Error

International units

from Randomization up to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Average Carbohydrate Factor (CarbF) Values

CarbF is calculated as 2.6 * weight (pounds) / total daily dose of insulin (grams per unit).

Posted

Least Squares Mean

Standard Error

grams per unit

Month 1 to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Average Correction Factor (CorrF) Values

CorrF is calculated as 1960 / total daily dose of insulin (milligrams/[deciliter*unit]).

Posted

Least Squares Mean

Standard Error

milligrams/(deciliter*unit)

Month 1 to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Average of Bolus Times Relative to Meal Times

The average meal bolus timing relative to meal time is defined as the minutes between the start time of a meal bolus and the start time of a meal.

Posted

Mean

Standard Deviation

minutes

Month 1 to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Average Glucose, Median Glucose, and Average Daily Standard Deviation

For each participant, the following continuous glucose monitoring (CGM) parameters were calculated using CGM values recorded after Randomization up to Month 12: average glucose, median glucose, and average daily standard deviation.

Posted

Least Squares Mean

Standard Error

milliliters per deciliter

Randomization to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Time Per Day <56 Milligrams Per Deciliter (mg/dL), ≤70 mg/dL, >70 mg/dL, <140 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL

For each participant, the following CGM parameters were calculated using CGM values recorded after Randomization up to Month 12: time per day spent in the pre-defined glucose classes.

Posted

Least Squares Mean

Standard Error

minutes

Randomization to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Area Per Day <56 mg/dL, ≤70 mg/dL, ≥140 mg/dL, Outside of 71 to 180 mg/dL, and Outside of 71 to 139 mg/dL

For each participant, the following continuous glucose monitoring (CGM) parameters were calculated using CGM values recorded after Randomization up to Month 12: area per day spent in the pre-defined glucose classes. The area per day for a specific glucose concentration range (e.g., <56 mg/dL) is the sum of the area under the curve with glucose concentration falling in the specific glucose concentration range (e.g., <56 mg/dL). For example, if the glucose stays constant at 50 mg/dL for the whole day (1,440 minutes), the area per day for glucose < 56 mg/dL equals: 50*1440 = 72,000 mg*minutes/dL.

Posted

Least Squares Mean

Standard Error

mg*minutes/deciliter

Randomization to Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001

Secondary

Change From Baseline in Weighted Impact ADDQoL Values at Month 12

The Audit of Diabetes Dependent Quality of Life (ADDQoL) is a validated, diabetes-specific questionnaire to evaluate the participant's assessment of quality of life (QoL). Participants rated the impact of diabetes on 19 applicable domains on a scale from -3 (maximum negative impact) to +3 (maximum positive impact) and then rated the importance of those domains for their QoL on a scale from 3 (very important) to 0 (not at all important). Impact ratings were multiplied by the corresponding importance ratings to provide a weighted-impact score for each domain from -9 (maximum negative impact) to +9 (maximum positive impact).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline; Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001

Secondary

Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12

The ADDQoL is a validated, diabetes-specific questionnaire to evaluate the participant's assessment of QoL. Participants rated the impact of diabetes on 19 applicable domains on a scale from -3 (maximum negative impact) to +3 (maximum positive impact) and then rated the importance of those domains for their QoL on a scale from 3 (very important) to 0 (not at all important). Impact ratings were multiplied by the corresponding importance ratings to provide a weighted-impact score for each domain from -9 (maximum negative impact) to +9 (maximum positive impact). Weighted impact scores were summed and divided by the number of applicable domains to give an overall Average Weighted Impact (AWI) score (higher values represent more positive impact). If there were less than 13 non-missing weighted-impact values, AWI was not to be calculated. Baseline is defined as the last measurement prior to randomization.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline; Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).

Secondary

Change From Baseline in DTSQs and DTSQc at Month 12

The Diabetes Treatment Satisfaction Questionnaire-status version (DTSQs) and DTSQ-change version (DTSQc) are validated tools to assess treatment satisfaction and change in treatment satisfaction after therapy changes have occurred. The scale total was computed by adding the 6 items (1, 4, 5, 6, 7, and 8) to produce the Treatment Satisfaction scale total, which has a minimum of 0 and a maximum of 36 on the DTSQs and a minimum of -18 and a maximum of 18 on the DTSQc. Higher scores represent greater satisfaction. If any of the 6 item scores were missing and the numbers of missing scores were less than the number of non-missing scores, the Treatment Satisfaction scale score was to be computed by taking the average of the existing scores and multiplying the average by 6. If there were less than 4 non-missing item scores, the Treatment Satisfaction scale score was not to be calculated. Baseline is defined as the last measurement prior to randomization.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline; Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).

Secondary

Mean Time to Change Infusion Site

Posted

Mean

Standard Deviation

minutes

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Mean Additional Time for Hylenex Pre-administration

Posted

Mean

Standard Deviation

minutes

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change

Posted

Count of Participants

Participants

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Number of Participants With the Indicated Responses to the Device Handling Questions

Participants were asked device handling questions to provide information about the impact of the Hylenex administration procedure on everyday life and to investigate perceptions of the overall efficacy and responsiveness of their insulin program. Question 1: Achieve excellent post meal glucose control; Question 2: Insulin responds quickly when basal rate is changed; Question 3: Insulin responds quickly when correction bolus is given.

Posted

Count of Participants

Participants

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Secondary

Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action

Posted

Mean

Standard Deviation

occurrences per week

Month 12

ID	Title	Description
OG000	Hylenex Recombinant	For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of Hylenex recombinant (either Formulation 1 or Formulation 2), delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
OG001	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Coronary artery disease	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Palpitations	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Vertigo	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Goitre	Endocrine disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hypogonadism	Endocrine disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Angle closure glaucoma	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Cataract	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Conjunctivitis	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Diabetic retinopathy	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dry eye	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Eye discharge	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Macular oedema	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Retinal haemorrhage	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Vitreous floaters	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Abdominal distention	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0023 affected113 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Constipation	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Dental caries	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Gastritis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Melaena	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Nausea	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0009 affected227 at risk EG0016 affected115 at risk EG0022 affected113 at risk
Periodontal disease	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Toothache	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Vomiting	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Application site erythema	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Chest discomfort	General disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Fatigue	General disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Feeling hot	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site bruising	General disorders	MedDRA (16.0)	Systematic Assessment		EG0005 affected227 at risk EG0013 affected115 at risk EG0020 affected113 at risk
Infusion site discomfort	General disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Infusion site erythema	General disorders	MedDRA (16.0)	Systematic Assessment		EG00012 affected227 at risk EG0014 affected115 at risk EG0021 affected113 at risk
Infusion site haematoma	General disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site haemorrhage	General disorders	MedDRA (16.0)	Systematic Assessment		EG0005 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Infusion site induration	General disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site oedema	General disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site pain	General disorders	MedDRA (16.0)	Systematic Assessment		EG00040 affected227 at risk EG00117 affected115 at risk EG0027 affected113 at risk
Infusion site paraesthesia	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site pruritus	General disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Infusion site scar	General disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site rash	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infusion site reaction	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Infusion site warmth	General disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Injection site pain	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Injury associated with device	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Localised oedema	General disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Non-cardiac chest pain	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Oedema peripheral	General disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Pyrexia	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (16.0)	Systematic Assessment	The Verbatim term for 1 participant was "Dilantin allergy" and the Verbatim term for the other participant was "Allergic reaction to Keflex and Bactrim".	EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hypersensitivity	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Seasonal allergy	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Abscess oral	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Acute sinusitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Atypical pneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Bacterial infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Bronchitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0005 affected227 at risk EG0015 affected115 at risk EG0023 affected113 at risk
Cellulitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Cystitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Ear infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0005 affected227 at risk EG0011 affected115 at risk EG0024 affected113 at risk
Eye infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Gastroenteritis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0014 affected115 at risk EG0021 affected113 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0015 affected115 at risk EG0020 affected113 at risk
Influenza	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0014 affected115 at risk EG0022 affected113 at risk
Infusion site infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Kidney infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Laryngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Localised infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Nail infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Nasopharyngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG00026 affected227 at risk EG0019 affected115 at risk EG0024 affected113 at risk
Oral herpes	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Oral infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Otitis media	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Paronychia	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Pharyngitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Pneumonia	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Rhinovirus infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Sialoadenitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Sinusitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG00012 affected227 at risk EG0017 affected115 at risk EG0028 affected113 at risk
Skin infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Tinea pedis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Tooth abscess	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Tooth infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG00031 affected227 at risk EG00115 affected115 at risk EG00213 affected113 at risk
Urinary tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG00010 affected227 at risk EG0013 affected115 at risk EG0023 affected113 at risk
Varicella	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Corneal abrasion	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Excoriation	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Foreign body in eye	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Incision cite erythema	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0012 affected115 at risk EG0023 affected113 at risk
Ligament rupture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Scar	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Skeletal injury	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Stress fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Blood glucose increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Blood potassium increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Blood triglycerides increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Fibrin D dimer increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Glycosylated haemoglobin increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Liver function test abnormal	Investigations	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Urine ketone body present	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Weight decreased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0013 affected115 at risk EG0020 affected113 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0013 affected115 at risk EG0020 affected113 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Muscle atrophy	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0012 affected115 at risk EG0024 affected113 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Spondylitis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Benign neoplasm of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Burning sensation	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Decreased vibratory sense	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0012 affected115 at risk EG0024 affected113 at risk
Hypoaesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Loss of consciousness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Migraine	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Nerve compression	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Paraesthesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Reflexes abnormal	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Sinus headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Syncope	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Tension headache	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Anxiety	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0012 affected115 at risk EG0022 affected113 at risk
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Depression	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG00010 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Insomnia	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Libido decreased	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Post-traumatic stress disorder	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Haematuria	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Proteinuria	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Pyelocaliectasis	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Pyuria	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Urethral pain	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Urinary retention	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Bartholin's cyst	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected122 at risk EG0011 affected53 at risk EG0020 affected64 at risk
Breast inflammation	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Breast pain	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Breast tenderness	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected122 at risk EG0010 affected53 at risk EG0021 affected64 at risk
Fibrocystic breast disease	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Menstruation irregular	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Pelvic floor muscle weakness	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected122 at risk EG0010 affected53 at risk EG0020 affected64 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected122 at risk EG0010 affected53 at risk EG0021 affected64 at risk
Uterine polyp	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected122 at risk EG0011 affected53 at risk EG0021 affected64 at risk
Allergic sinusitis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0015 affected115 at risk EG0024 affected113 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0014 affected115 at risk EG0020 affected113 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0013 affected115 at risk EG0021 affected113 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0013 affected115 at risk EG0023 affected113 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0002 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Chronic spontaneous urticaria	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0006 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Ingrowing Nail	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Lipohypertrophy	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Onychomadesis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0005 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Scab	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Skin mass	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Menopause	Social circumstances	MedDRA (16.0)	Systematic Assessment		EG0001 affected122 at risk EG0010 affected53 at risk EG0020 affected64 at risk
Aortic arteriosclerosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hypertension	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0004 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Hypotension	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Varicose vein	Vascular disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Chest pain	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Abscess limb	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Convulsion	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Bradycardia	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Tachycardia	Cardiac disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Eustachian tube dysfunction	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Otorrhoea	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Hypothyroidism	Endocrine disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Eye haemorrhage	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Vitreous haemorrhage	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Coeliac disease	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Tooth impacted	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Hunger	General disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Biliary colic	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Cholestasis	Hepatobiliary disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Allergy to chemicals	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Allergy to metals	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Bronchitis viral	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Enteritis infectious	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Eye infection viral	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Fungal infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Gastrointestinal infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Gastrointestinal viral infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0003 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
H1N1 Influenza	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Herpes zoster	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Hordeolum	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Infectious mononucleosis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Mastoiditis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Mycobacteriuim abscessus infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Oral candidiasis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Pilonidal cyst	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Rhinitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Staphylococcal skin infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Tonsillitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Fascial rupture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Foreign body	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Alanine aminotransferase increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Blood bilirubin increased	Investigations	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Carotid bruit	Investigations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Tetany	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Bunion	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Exostosis	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0022 affected113 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Knuckle pads	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Morton's neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Amnesia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dizziness	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Neuralgia	Nervous system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Binge eating	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Panic attack	Psychiatric disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Calculus bladder	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Vulvovaginal pruritus	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Scar pain	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Stasis dermatitis	Skin and subcutaneous tissue disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Wisdom teeth removal	Surgical and medical procedures	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Sarcoidosis	Immune system disorders	MedDRA (16.0)	Systematic Assessment		EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Keratitis	Eye disorders	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Candidiasis	Infections and infestations	MedDRA (16.0)	Systematic Assessment		EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk

ID	Title	Description
BG000	Commercial Hylenex Recombinant (Formulation 1)	Hylenex Formulation 1: For 12 months, participants received their regular treatment of rapid-acting continuous CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
BG001	Precommercial Hylenex Recombinant (Formulation 2)	Hylenex Formulation 2: For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).
BG002	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.
BG003	Total	Total of all reporting groups

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C515423	Akacid-medical-formulation
D061268	Insulin Lispro
D061267	Insulin Aspart
C479079	insulin glulisine

ID	Term
D061266	Insulin, Short-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Commercial Hylenex Recombinant (Formulation 1)	Hylenex Formulation 1: For 12 months, participants received their regular treatment of rapid-acting continuous CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).	11	227	174	227
EG001	Precommercial Hylenex Recombinant (Formulation 2)	Hylenex Formulation 2: For 12 months, participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the precommercial form of Hylenex recombinant, delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).	10	115	84	115
EG002	Standard Rapid-Acting Insulin CSII	Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.	13	113	76	113

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Coronary artery disease	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0023 affected113 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Retinal detachment	Eye disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Appendicitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0021 affected113 at risk
Viral infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0012 affected115 at risk EG0021 affected113 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0003 affected227 at risk EG0011 affected115 at risk EG0022 affected113 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Convulsion	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Pelvic floor muscle weakness	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected122 at risk EG0010 affected53 at risk EG0020 affected64 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Arteriosclerosis	Vascular disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Chest pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Non-cardiac chest pain	General disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0012 affected115 at risk EG0020 affected113 at risk
Abscess limb	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Cellulitis	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Influenza	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Postoperative wound infection	Infections and infestations	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Stiff person syndrome	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Syncope	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0010 affected115 at risk EG0021 affected113 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (16.0)	Systematic Assessment	EG0001 affected227 at risk EG0010 affected115 at risk EG0020 affected113 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk
Menometrorrhagia	Reproductive system and breast disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected122 at risk EG0010 affected53 at risk EG0021 affected64 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.0)	Systematic Assessment	EG0000 affected227 at risk EG0011 affected115 at risk EG0020 affected113 at risk