Trial Outcomes & Findings for CONSISTENT 1: Metabolic and Safety Outcomes of Hylenex Recombinant (Hyaluronidase Human Injection) Preadministered at CSII Infusion Site in Participants With Type 1 Diabetes Mellitus (T1DM) (NCT NCT01848990)

NCT ID: NCT01848990

Last Updated: 2018-11-07

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

456 participants

Primary outcome timeframe

Baseline; 6 Months

Results posted on

2018-11-07

Participant Flow

Participant milestones

Participant milestones
Measure	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).	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).	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.
Overall Study STARTED	227	115	114
Overall Study Received at Least 1 Dose of Study Drug	227	115	113
Overall Study Completed Month 6	194	106	103
Overall Study COMPLETED	181	95	98
Overall Study NOT COMPLETED	46	20	16

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).	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.
Overall Study Adverse Event	6	2	0
Overall Study Lost to Follow-up	6	2	2
Overall Study Protocol Violation	1	1	0
Overall Study Withdrawal by Subject	29	10	11
Overall Study Physician Decision	1	1	0
Overall Study Non Compliance	1	0	0
Overall Study Death	1	0	1
Overall Study Other	1	4	2

Baseline Characteristics

CONSISTENT 1: Metabolic and Safety Outcomes of Hylenex Recombinant (Hyaluronidase Human Injection) Preadministered at CSII Infusion Site in Participants With Type 1 Diabetes Mellitus (T1DM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Commercial Hylenex Recombinant (Formulation 1) n=227 Participants 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).	Precommercial Hylenex Recombinant (Formulation 2) n=115 Participants 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).	Standard Rapid-Acting Insulin CSII n=113 Participants Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.	Total n=455 Participants Total of all reporting groups
Age, Continuous	47.5 years STANDARD_DEVIATION 12.90 • n=5 Participants	45.9 years STANDARD_DEVIATION 13.14 • n=7 Participants	49.7 years STANDARD_DEVIATION 14.73 • n=5 Participants	47.6 years STANDARD_DEVIATION 13.47 • n=4 Participants
Sex: Female, Male Female	122 Participants n=5 Participants	53 Participants n=7 Participants	64 Participants n=5 Participants	239 Participants n=4 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	62 Participants n=7 Participants	49 Participants n=5 Participants	216 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	217 Participants n=5 Participants	108 Participants n=7 Participants	108 Participants n=5 Participants	433 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	8 participants n=5 Participants	3 participants n=7 Participants	2 participants n=5 Participants	13 participants n=4 Participants
Race/Ethnicity, Customized White	216 participants n=5 Participants	112 participants n=7 Participants	107 participants n=5 Participants	435 participants n=4 Participants
Race/Ethnicity, Customized Asian Indian	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment United States	227 participants n=5 Participants	115 participants n=7 Participants	113 participants n=5 Participants	455 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline; 6 Months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=296 Participants 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).	Standard Rapid-Acting Insulin CSII n=103 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)	-0.14 percentage of HbA1c Standard Deviation 0.521	-0.18 percentage of HbA1c Standard Deviation 0.687

PRIMARY outcome

Timeframe: Baseline; 12 Months

Population: 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.

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

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=268 Participants 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).	Standard Rapid-Acting Insulin CSII n=95 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline to 12 Months in HbA1c	-0.13 percentage of HbA1c Standard Deviation 0.590	-0.26 percentage of HbA1c Standard Deviation 0.718

SECONDARY outcome

Timeframe: After Month 1 up to Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=184 Participants 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).	Standard Rapid-Acting Insulin CSII n=63 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Rates of Hypoglycemia Events (HE) to Month 6 <56 mg/dL	2.9103 events per participant per month	4.1970 events per participant per month
Rates of Hypoglycemia Events (HE) to Month 6 ≤70 mg/dL	11.6219 events per participant per month	14.7112 events per participant per month
Rates of Hypoglycemia Events (HE) to Month 6 Nocturnal HEs	1.6224 events per participant per month	2.0727 events per participant per month
Rates of Hypoglycemia Events (HE) to Month 6 Severe HEs	0.0055 events per participant per month	0.0160 events per participant per month

SECONDARY outcome

Timeframe: After Month 1 up to Month 12

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

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Rates of HEs to Month 12 <56 mg/dL	2.6792 events per participant per month	3.3022 events per participant per month
Rates of HEs to Month 12 ≤70 mg/dL	11.3803 events per participant per month	12.3591 events per participant per month
Rates of HEs to Month 12 Nocturnal HEs	1.6754 events per participant per month	1.9203 events per participant per month
Rates of HEs to Month 12 Severe HEs	0.0091 events per participant per month	0.0085 events per participant per month

SECONDARY outcome

Timeframe: After Month 1 up to Month 6

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

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=298 Participants 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).	Standard Rapid-Acting Insulin CSII n=103 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Rates of Hyperglycemia Events to Month 6 >240 mg/dL	18.0422 events per participant per month	18.4696 events per participant per month
Rates of Hyperglycemia Events to Month 6 >300 mg/dL	6.4768 events per participant per month	6.8155 events per participant per month

SECONDARY outcome

Timeframe: After Month 1 up to Month 12

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

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Rates of Hyperglycemia Events to Month 12 >300 mg/dL	7.1138 events per participant per month	6.8900 events per participant per month
Rates of Hyperglycemia Events to Month 12 >240 mg/dL	18.9784 events per participant per month	18.2785 events per participant per month

SECONDARY outcome

Timeframe: After Month 1 up to Month 6

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

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=184 Participants 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).	Standard Rapid-Acting Insulin CSII n=63 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Mean Glucose Excursions at 6 Months Breakfast	17.3 milligrams per deciliter (mg/dL) Standard Error 2.77	20.7 milligrams per deciliter (mg/dL) Standard Error 4.76
Mean Glucose Excursions at 6 Months Lunch	22.2 milligrams per deciliter (mg/dL) Standard Error 2.67	17.9 milligrams per deciliter (mg/dL) Standard Error 4.58
Mean Glucose Excursions at 6 Months Dinner	12.6 milligrams per deciliter (mg/dL) Standard Error 2.45	12.5 milligrams per deciliter (mg/dL) Standard Error 4.18
Mean Glucose Excursions at 6 Months Overall	17.1 milligrams per deciliter (mg/dL) Standard Error 1.70	16.9 milligrams per deciliter (mg/dL) Standard Error 2.91

SECONDARY outcome

Timeframe: After Month 1 up to Month 12

Population: ITT Population. Only participants with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=200 Participants 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).	Standard Rapid-Acting Insulin CSII n=63 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Mean Glucose Excursions at 12 Months Breakfast	20.1 milligrams per deciliter (mg/dL) Standard Error 2.36	24.9 milligrams per deciliter (mg/dL) Standard Error 4.21
Mean Glucose Excursions at 12 Months Lunch	22.4 milligrams per deciliter (mg/dL) Standard Error 2.17	21.0 milligrams per deciliter (mg/dL) Standard Error 3.89
Mean Glucose Excursions at 12 Months Dinner	12.7 milligrams per deciliter (mg/dL) Standard Error 2.08	13.8 milligrams per deciliter (mg/dL) Standard Error 3.69
Mean Glucose Excursions at 12 Months Overall	17.1 milligrams per deciliter (mg/dL) Standard Error 1.49	19.7 milligrams per deciliter (mg/dL) Standard Error 2.65

SECONDARY outcome

Timeframe: After Month 1 up to Month 6

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

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=184 Participants 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).	Standard Rapid-Acting Insulin CSII n=63 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months	70.9 mg/dL Standard Error 1.09	72.2 mg/dL Standard Error 1.86

SECONDARY outcome

Timeframe: After Month 1 up to Month 12

Population: ITT Population. Only participants with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=200 Participants 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).	Standard Rapid-Acting Insulin CSII n=63 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months	72.9 mg/dL Standard Error 1.04	72.4 mg/dL Standard Error 1.85

SECONDARY outcome

Timeframe: Month 12

Population: 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.

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

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=268 Participants 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).	Standard Rapid-Acting Insulin CSII n=95 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12 HbA1c <7.0%	61 Participants	21 Participants
Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12 HbA1c ≤6.5%	18 Participants	6 Participants

SECONDARY outcome

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

Baseline is defined as the last measurement prior to randomization.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline in Body Weight to Month 12 Week 2	-0.10 kilograms Standard Deviation 1.272	0.19 kilograms Standard Deviation 1.257
Change From Baseline in Body Weight to Month 12 Month 1	-0.11 kilograms Standard Deviation 1.583	0.20 kilograms Standard Deviation 1.696
Change From Baseline in Body Weight to Month 12 Month 2	-0.03 kilograms Standard Deviation 2.002	0.48 kilograms Standard Deviation 1.672
Change From Baseline in Body Weight to Month 12 Month 3	0.16 kilograms Standard Deviation 2.562	0.37 kilograms Standard Deviation 1.858
Change From Baseline in Body Weight to Month 12 Month 4	0.04 kilograms Standard Deviation 2.680	0.37 kilograms Standard Deviation 2.230
Change From Baseline in Body Weight to Month 12 Month 6	0.60 kilograms Standard Deviation 3.035	0.83 kilograms Standard Deviation 2.287
Change From Baseline in Body Weight to Month 12 Month 9	0.91 kilograms Standard Deviation 3.355	0.92 kilograms Standard Deviation 3.033
Change From Baseline in Body Weight to Month 12 Month 12	0.61 kilograms Standard Deviation 3.796	0.48 kilograms Standard Deviation 4.078

SECONDARY outcome

Timeframe: from Randomization up to Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=327 Participants 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).	Standard Rapid-Acting Insulin CSII n=111 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Average of Daily Insulin Doses (Bolus, Basal, and Total) Daily bolus dose	21.9 International units Standard Error 0.78	22.9 International units Standard Error 1.33
Average of Daily Insulin Doses (Bolus, Basal, and Total) Daily basal dose	28.0 International units Standard Error 0.73	25.7 International units Standard Error 1.26
Average of Daily Insulin Doses (Bolus, Basal, and Total) Daily total dose	49.9 International units Standard Error 1.32	48.5 International units Standard Error 2.27

SECONDARY outcome

Timeframe: Month 1 to Month 12

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

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=304 Participants 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).	Standard Rapid-Acting Insulin CSII n=100 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Average Carbohydrate Factor (CarbF) Values	11.1 grams per unit Standard Error 0.26	11.0 grams per unit Standard Error 0.46

SECONDARY outcome

Timeframe: Month 1 to Month 12

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

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=299 Participants 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).	Standard Rapid-Acting Insulin CSII n=101 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Average Correction Factor (CorrF) Values	43.2 milligrams/(deciliter*unit) Standard Error 1.06	45.3 milligrams/(deciliter*unit) Standard Error 1.83

SECONDARY outcome

Timeframe: Month 1 to Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Average of Bolus Times Relative to Meal Times Breakfast	-2.3 minutes Standard Deviation 8.17	-3.9 minutes Standard Deviation 7.83
Average of Bolus Times Relative to Meal Times Lunch	-1.8 minutes Standard Deviation 6.75	-1.6 minutes Standard Deviation 8.61
Average of Bolus Times Relative to Meal Times Dinner	-1.7 minutes Standard Deviation 7.48	-1.7 minutes Standard Deviation 9.19
Average of Bolus Times Relative to Meal Times Overall	-1.9 minutes Standard Deviation 6.51	-2.4 minutes Standard Deviation 7.86

SECONDARY outcome

Timeframe: Randomization to Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=80 Participants 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).	Standard Rapid-Acting Insulin CSII n=30 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Average Glucose, Median Glucose, and Average Daily Standard Deviation Average glucose	152.9 milliliters per deciliter Standard Error 1.79	151.9 milliliters per deciliter Standard Error 2.93
Average Glucose, Median Glucose, and Average Daily Standard Deviation Median glucose	145.2 milliliters per deciliter Standard Error 1.80	143.4 milliliters per deciliter Standard Error 2.94
Average Glucose, Median Glucose, and Average Daily Standard Deviation Average daily standard deviation	48.9 milliliters per deciliter Standard Error 0.85	49.7 milliliters per deciliter Standard Error 1.39

SECONDARY outcome

Timeframe: Randomization to Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=80 Participants 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).	Standard Rapid-Acting Insulin CSII n=30 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
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 Time per day <56 mg/dL	18.1 minutes Standard Error 2.40	20.3 minutes Standard Error 3.91
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 Time per day ≤70 mg/dL	63.0 minutes Standard Error 5.37	68.5 minutes Standard Error 8.77
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 Time per day >70 mg/dL	1358.8 minutes Standard Error 5.62	1351.9 minutes Standard Error 9.18
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 Time per day <140 mg/dL	660.3 minutes Standard Error 16.99	683.7 minutes Standard Error 27.74
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 Time per day ≥140 mg/dL	756.4 minutes Standard Error 17.02	732.5 minutes Standard Error 27.80
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 Time per day outside of 71 to 180 mg/dL	464.4 minutes Standard Error 15.02	461.7 minutes Standard Error 24.54
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 Time per day outside of 71 to139 mg/dL	819.4 minutes Standard Error 14.74	801.0 minutes Standard Error 24.07

SECONDARY outcome

Timeframe: Randomization to Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=80 Participants 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).	Standard Rapid-Acting Insulin CSII n=30 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
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 Area per day <56 mg/dL	129.7 mg*minutes/deciliter Standard Error 21.71	163.2 mg*minutes/deciliter Standard Error 35.45
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 Area per day ≤70 mg/dL	687.0 mg*minutes/deciliter Standard Error 77.58	771.7 mg*minutes/deciliter Standard Error 126.69
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 Area per day ≥140 mg/dL	42660.2 mg*minutes/deciliter Standard Error 1874.62	42317.2 mg*minutes/deciliter Standard Error 3061.24
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 Area per day outside of 71 to 180 mg/dL	20033.8 mg*minutes/deciliter Standard Error 1232.60	20411.2 mg*minutes/deciliter Standard Error 2012.83
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 Area per day outside of 71 to 139 mg/dL	43347.2 mg*minutes/deciliter Standard Error 1857.54	43089.0 mg*minutes/deciliter Standard Error 3033.35

SECONDARY outcome

Timeframe: Baseline; 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).

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Leisure activities	-0.2 score on a scale Standard Error 0.14	0.0 score on a scale Standard Error 0.24
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Work life	-0.1 score on a scale Standard Error 0.15	0.0 score on a scale Standard Error 0.27
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Local or long distance travel	-0.4 score on a scale Standard Error 0.15	-0.2 score on a scale Standard Error 0.25
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Vacations	0.0 score on a scale Standard Error 0.15	0.2 score on a scale Standard Error 0.25
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Do physically	-0.1 score on a scale Standard Error 0.14	-0.2 score on a scale Standard Error 0.23
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Family life	0.2 score on a scale Standard Error 0.14	0.1 score on a scale Standard Error 0.23
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Friendships and social life	0.3 score on a scale Standard Error 0.13	0.1 score on a scale Standard Error 0.22
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Close personal relationship	0.1 score on a scale Standard Error 0.16	0.1 score on a scale Standard Error 0.27
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Sex life	0.0 score on a scale Standard Error 0.14	-0.3 score on a scale Standard Error 0.24
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Physical appearance	0.1 score on a scale Standard Error 0.11	-0.2 score on a scale Standard Error 0.19
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Self-confidence	0.0 score on a scale Standard Error 0.12	-0.1 score on a scale Standard Error 0.21
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Motivation	0.0 score on a scale Standard Error 0.14	0.3 score on a scale Standard Error 0.24
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 The way people in general react	0.2 score on a scale Standard Error 0.10	-0.1 score on a scale Standard Error 0.17
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Feelings about the future	-0.1 score on a scale Standard Error 0.16	0.3 score on a scale Standard Error 0.26
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Financial situation	0.1 score on a scale Standard Error 0.14	0.0 score on a scale Standard Error 0.23
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Living situation and conditions	0.0 score on a scale Standard Error 0.13	-0.1 score on a scale Standard Error 0.22
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Depend on others	-0.1 score on a scale Standard Error 0.17	0.4 score on a scale Standard Error 0.28
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Freedom to eat	0.0 score on a scale Standard Error 0.15	-0.3 score on a scale Standard Error 0.25
Change From Baseline in Weighted Impact ADDQoL Values at Month 12 Freedom to drink	-0.2 score on a scale Standard Error 0.14	-0.3 score on a scale Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline; 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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=265 Participants 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).	Standard Rapid-Acting Insulin CSII n=95 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12	0.0 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline; 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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=342 Participants 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).	Standard Rapid-Acting Insulin CSII n=114 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Change From Baseline in DTSQs and DTSQc at Month 12 DTSQs	0.0 score on a scale Standard Error 0.32	0.0 score on a scale Standard Error 0.53
Change From Baseline in DTSQs and DTSQc at Month 12 DTSQc	9.4 score on a scale Standard Error 0.40	9.4 score on a scale Standard Error 0.68

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=276 Participants 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).	Standard Rapid-Acting Insulin CSII n=97 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Mean Time to Change Infusion Site	5.7 minutes Standard Deviation 4.45	4.7 minutes Standard Deviation 3.68

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=276 Participants 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).	Standard Rapid-Acting Insulin CSII n=37 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Mean Additional Time for Hylenex Pre-administration	2.9 minutes Standard Deviation 3.96	3.8 minutes Standard Deviation 2.84

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=276 Participants 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).	Standard Rapid-Acting Insulin CSII n=97 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change Very easy	143 Participants	49 Participants
Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change Easy	130 Participants	46 Participants
Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change Difficult	3 Participants	1 Participants
Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change Very difficult	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Month 12

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.

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=276 Participants 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).	Standard Rapid-Acting Insulin CSII n=97 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Number of Participants With the Indicated Responses to the Device Handling Questions Question 1 · Completely agree	5 Participants	0 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 1 · Agree	110 Participants	28 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 1 · Neither agree or disagree	97 Participants	44 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 1 · Disagree	59 Participants	22 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 1 · Completely disagree	5 Participants	3 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 2 · Completely agree	31 Participants	8 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 2 · Agree	146 Participants	48 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 2 · Neither agree or disagree	71 Participants	28 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 2 · Disagree	25 Participants	12 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 2 · Completely disagree	3 Participants	1 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 3 · Completely agree	36 Participants	14 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 3 · Agree	165 Participants	39 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 3 · Neither agree or disagree	34 Participants	22 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 3 · Disagree	38 Participants	20 Participants
Number of Participants With the Indicated Responses to the Device Handling Questions Question 3 · Completely disagree	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Month 12

Outcome measures

Outcome measures
Measure	Hylenex Recombinant n=275 Participants 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).	Standard Rapid-Acting Insulin CSII n=97 Participants Participants received their regular treatment of rapid-acting insulin CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.
Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action	2.1 occurrences per week Standard Deviation 2.19	2.5 occurrences per week Standard Deviation 2.37

Adverse Events

Commercial Hylenex Recombinant (Formulation 1)

Serious events: 11 serious events

Other events: 174 other events

Deaths: 0 deaths

Precommercial Hylenex Recombinant (Formulation 2)

Serious events: 10 serious events

Other events: 84 other events

Deaths: 0 deaths

Standard Rapid-Acting Insulin CSII

Serious events: 13 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Commercial Hylenex Recombinant (Formulation 1) n=227 participants at risk 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).	Precommercial Hylenex Recombinant (Formulation 2) n=115 participants at risk 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).	Standard Rapid-Acting Insulin CSII n=113 participants at risk Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.
Cardiac disorders Angina pectoris	0.00% 0/227	0.00% 0/115	0.88% 1/113
Cardiac disorders Coronary artery disease	0.00% 0/227	0.00% 0/115	2.7% 3/113
Ear and labyrinth disorders Vertigo positional	0.00% 0/227	0.00% 0/115	0.88% 1/113
Eye disorders Retinal detachment	0.00% 0/227	0.00% 0/115	0.88% 1/113
Gastrointestinal disorders Oesophagitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Appendicitis	0.00% 0/227	0.87% 1/115	0.88% 1/113
Infections and infestations Viral infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Spinal fracture	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Diabetic ketoacidosis	0.44% 1/227	1.7% 2/115	0.88% 1/113
Metabolism and nutrition disorders Hypoglycaemia	1.3% 3/227	0.87% 1/115	1.8% 2/113
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/227	0.00% 0/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Convulsion	0.00% 0/227	0.87% 1/115	0.00% 0/113
Reproductive system and breast disorders Pelvic floor muscle weakness	0.82% 1/122	0.00% 0/53	0.00% 0/64
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/227	0.87% 1/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/227	0.00% 0/115	0.88% 1/113
Vascular disorders Arteriosclerosis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Cardiac disorders Acute myocardial infarction	0.00% 0/227	0.00% 0/115	0.88% 1/113
General disorders Chest pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
General disorders Non-cardiac chest pain	0.00% 0/227	1.7% 2/115	0.00% 0/113
Infections and infestations Abscess limb	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Cellulitis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Influenza	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Postoperative wound infection	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Procedural pain	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Dehydration	0.00% 0/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Stiff person syndrome	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Syncope	0.00% 0/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Transient ischaemic attack	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Nephrolithiasis	0.00% 0/227	0.87% 1/115	0.00% 0/113
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/122	0.00% 0/53	1.6% 1/64
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/227	0.87% 1/115	0.00% 0/113

Other adverse events

Other adverse events
Measure	Commercial Hylenex Recombinant (Formulation 1) n=227 participants at risk 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).	Precommercial Hylenex Recombinant (Formulation 2) n=115 participants at risk 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).	Standard Rapid-Acting Insulin CSII n=113 participants at risk Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 12 months.
Respiratory, thoracic and mediastinal disorders Asthma	1.3% 3/227	0.87% 1/115	0.00% 0/113
Renal and urinary disorders Haematuria	0.44% 1/227	0.87% 1/115	0.00% 0/113
Psychiatric disorders Post-traumatic stress disorder	0.44% 1/227	0.00% 0/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Atelectasis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Mastoiditis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Gastrointestinal disorders Irritable bowel syndrome	0.44% 1/227	0.87% 1/115	0.88% 1/113
Gastrointestinal disorders Melaena	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Nausea	4.0% 9/227	5.2% 6/115	1.8% 2/113
Gastrointestinal disorders Periodontal disease	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Toothache	0.88% 2/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Vomiting	2.6% 6/227	0.87% 1/115	1.8% 2/113
General disorders Application site erythema	0.44% 1/227	0.00% 0/115	0.00% 0/113
General disorders Chest discomfort	0.00% 0/227	0.87% 1/115	0.00% 0/113
General disorders Fatigue	1.3% 3/227	1.7% 2/115	0.88% 1/113
General disorders Feeling hot	0.44% 1/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site bruising	2.2% 5/227	2.6% 3/115	0.00% 0/113
General disorders Infusion site discomfort	0.00% 0/227	0.87% 1/115	0.00% 0/113
General disorders Infusion site erythema	5.3% 12/227	3.5% 4/115	0.88% 1/113
General disorders Infusion site haematoma	0.88% 2/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site haemorrhage	2.2% 5/227	1.7% 2/115	0.00% 0/113
General disorders Infusion site induration	1.8% 4/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site oedema	0.88% 2/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site pain	17.6% 40/227	14.8% 17/115	6.2% 7/113
General disorders Infusion site paraesthesia	0.44% 1/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site pruritus	1.8% 4/227	1.7% 2/115	0.00% 0/113
General disorders Infusion site scar	0.88% 2/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site rash	0.44% 1/227	0.00% 0/115	0.00% 0/113
General disorders Infusion site reaction	0.44% 1/227	0.87% 1/115	0.88% 1/113
General disorders Infusion site warmth	0.88% 2/227	0.00% 0/115	0.00% 0/113
General disorders Injection site pain	0.44% 1/227	0.87% 1/115	0.00% 0/113
General disorders Injury associated with device	0.44% 1/227	0.00% 0/115	0.00% 0/113
General disorders Localised oedema	0.00% 0/227	0.00% 0/115	0.88% 1/113
General disorders Non-cardiac chest pain	0.44% 1/227	0.87% 1/115	0.00% 0/113
General disorders Oedema peripheral	1.3% 3/227	1.7% 2/115	0.88% 1/113
General disorders Pyrexia	0.44% 1/227	0.87% 1/115	0.88% 1/113
Hepatobiliary disorders Cholecystitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Immune system disorders Drug hypersensitivity	1.3% 3/227	0.00% 0/115	0.00% 0/113
Immune system disorders Hypersensitivity	0.00% 0/227	0.00% 0/115	0.88% 1/113
Immune system disorders Seasonal allergy	0.88% 2/227	0.87% 1/115	0.00% 0/113
Infections and infestations Abscess oral	0.00% 0/227	0.87% 1/115	0.88% 1/113
Infections and infestations Acute sinusitis	0.00% 0/227	0.00% 0/115	1.8% 2/113
Infections and infestations Atypical pneumonia	0.44% 1/227	0.87% 1/115	0.00% 0/113
Infections and infestations Bacterial infection	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Bronchitis	2.2% 5/227	4.3% 5/115	2.7% 3/113
Infections and infestations Cellulitis	0.88% 2/227	0.00% 0/115	0.88% 1/113
Infections and infestations Cystitis	1.3% 3/227	0.87% 1/115	0.88% 1/113
Infections and infestations Ear infection	2.2% 5/227	0.87% 1/115	3.5% 4/113
Infections and infestations Eye infection	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Gastroenteritis	1.8% 4/227	3.5% 4/115	0.88% 1/113
Infections and infestations Gastroenteritis viral	0.88% 2/227	4.3% 5/115	0.00% 0/113
Infections and infestations Influenza	2.6% 6/227	3.5% 4/115	1.8% 2/113
Infections and infestations Infusion site infection	0.88% 2/227	0.87% 1/115	0.88% 1/113
Infections and infestations Kidney infection	0.44% 1/227	0.87% 1/115	0.00% 0/113
Infections and infestations Laryngitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Localised infection	0.88% 2/227	0.87% 1/115	1.8% 2/113
Infections and infestations Lower respiratory tract infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Nail infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Nasopharyngitis	11.5% 26/227	7.8% 9/115	3.5% 4/113
Infections and infestations Oral herpes	0.44% 1/227	0.87% 1/115	0.00% 0/113
Infections and infestations Oral infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Otitis media	0.44% 1/227	0.87% 1/115	0.88% 1/113
Infections and infestations Paronychia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Pharyngitis	0.44% 1/227	0.00% 0/115	1.8% 2/113
Infections and infestations Pharyngitis streptococcal	0.44% 1/227	0.87% 1/115	1.8% 2/113
Infections and infestations Pneumonia	0.44% 1/227	0.00% 0/115	0.88% 1/113
Infections and infestations Respiratory tract infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Respiratory tract infection viral	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Rhinovirus infection	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Sialoadenitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Sinusitis	5.3% 12/227	6.1% 7/115	7.1% 8/113
Infections and infestations Skin infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Tinea pedis	0.44% 1/227	0.87% 1/115	0.00% 0/113
Infections and infestations Tooth abscess	0.44% 1/227	0.00% 0/115	0.88% 1/113
Infections and infestations Tooth infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Upper respiratory tract infection	13.7% 31/227	13.0% 15/115	11.5% 13/113
Infections and infestations Urinary tract infection	4.4% 10/227	2.6% 3/115	2.7% 3/113
Infections and infestations Varicella	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Vulvovaginal mycotic infection	0.00% 0/227	1.7% 2/115	0.88% 1/113
Injury, poisoning and procedural complications Animal bite	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Arthropod bite	0.44% 1/227	0.87% 1/115	1.8% 2/113
Injury, poisoning and procedural complications Concussion	0.88% 2/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Corneal abrasion	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Epicondylitis	0.44% 1/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Excoriation	0.44% 1/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Foot fracture	1.8% 4/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Foreign body in eye	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Hand fracture	0.00% 0/227	0.00% 0/115	1.8% 2/113
Injury, poisoning and procedural complications Incision cite erythema	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Joint injury	1.3% 3/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Laceration	0.44% 1/227	1.7% 2/115	2.7% 3/113
Injury, poisoning and procedural complications Ligament rupture	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Ligament sprain	1.8% 4/227	0.87% 1/115	0.88% 1/113
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Muscle strain	0.88% 2/227	0.87% 1/115	0.88% 1/113
Injury, poisoning and procedural complications Procedural pain	1.3% 3/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Road traffic accident	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Scar	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Skeletal injury	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Stress fracture	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Thermal burn	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Tooth fracture	0.88% 2/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Traumatic haematoma	0.44% 1/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Upper limb fracture	0.44% 1/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Wrist fracture	0.44% 1/227	0.00% 0/115	0.00% 0/113
Investigations Aspartate aminotransferase increased	0.00% 0/227	0.00% 0/115	1.8% 2/113
Investigations Blood alkaline phosphatase increased	0.00% 0/227	0.00% 0/115	0.88% 1/113
Investigations Blood glucose increased	0.00% 0/227	0.00% 0/115	0.88% 1/113
Investigations Blood potassium increased	0.00% 0/227	0.87% 1/115	0.00% 0/113
Investigations Blood triglycerides increased	0.44% 1/227	0.00% 0/115	0.00% 0/113
Investigations Fibrin D dimer increased	0.44% 1/227	0.00% 0/115	0.00% 0/113
Investigations Glycosylated haemoglobin increased	0.44% 1/227	0.00% 0/115	0.88% 1/113
Investigations Liver function test abnormal	0.88% 2/227	0.00% 0/115	0.00% 0/113
Investigations Urine ketone body present	0.44% 1/227	0.00% 0/115	0.00% 0/113
Investigations Weight decreased	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Dehydration	0.00% 0/227	0.87% 1/115	0.00% 0/113
Metabolism and nutrition disorders Diabetic ketoacidosis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Hyperglycaemia	0.88% 2/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Hyperlipidaemia	0.44% 1/227	0.87% 1/115	0.00% 0/113
Metabolism and nutrition disorders Hypocalcaemia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Hyponatraemia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Vitamin D deficiency	0.44% 1/227	0.87% 1/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Arthralgia	1.8% 4/227	2.6% 3/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Back pain	2.6% 6/227	2.6% 3/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Bursitis	0.88% 2/227	0.00% 0/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Costochondritis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Dupuytren's contracture	0.44% 1/227	0.00% 0/115	1.8% 2/113
Musculoskeletal and connective tissue disorders Fibromyalgia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Flank pain	0.44% 1/227	1.7% 2/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.8% 4/227	0.87% 1/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Joint swelling	1.3% 3/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Muscle atrophy	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Muscle spasms	1.3% 3/227	1.7% 2/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.8% 4/227	0.87% 1/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Myalgia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Neck pain	1.8% 4/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Pain in extremity	0.88% 2/227	1.7% 2/115	3.5% 4/113
Musculoskeletal and connective tissue disorders Periarthritis	1.3% 3/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.88% 2/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Spondylitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Tendonitis	0.44% 1/227	0.87% 1/115	0.88% 1/113
Musculoskeletal and connective tissue disorders Trigger finger	1.3% 3/227	1.7% 2/115	0.00% 0/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Carpal tunnel syndrome	1.8% 4/227	0.00% 0/115	0.88% 1/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.44% 1/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Burning sensation	0.44% 1/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Cervicobrachial syndrome	0.88% 2/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Decreased vibratory sense	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Headache	2.6% 6/227	1.7% 2/115	3.5% 4/113
Nervous system disorders Hypoaesthesia	0.88% 2/227	0.00% 0/115	1.8% 2/113
Nervous system disorders Loss of consciousness	0.00% 0/227	0.00% 0/115	1.8% 2/113
Nervous system disorders Migraine	0.44% 1/227	0.87% 1/115	0.88% 1/113
Nervous system disorders Nerve compression	0.44% 1/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Neuropathy peripheral	1.3% 3/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Paraesthesia	0.44% 1/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Reflexes abnormal	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Sinus headache	0.44% 1/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Syncope	0.44% 1/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Tension headache	0.44% 1/227	0.00% 0/115	0.88% 1/113
Psychiatric disorders Anxiety	0.88% 2/227	1.7% 2/115	1.8% 2/113
Psychiatric disorders Attention deficit/hyperactivity disorder	0.00% 0/227	0.87% 1/115	0.00% 0/113
Psychiatric disorders Depression	4.4% 10/227	1.7% 2/115	0.88% 1/113
Psychiatric disorders Insomnia	1.3% 3/227	0.87% 1/115	0.00% 0/113
Psychiatric disorders Libido decreased	0.00% 0/227	0.00% 0/115	0.88% 1/113
Renal and urinary disorders Nephrolithiasis	0.44% 1/227	0.00% 0/115	0.88% 1/113
Renal and urinary disorders Proteinuria	0.00% 0/227	0.87% 1/115	0.88% 1/113
Renal and urinary disorders Pyelocaliectasis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Pyuria	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Renal failure acute	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Stress urinary incontinence	0.00% 0/227	0.00% 0/115	0.88% 1/113
Renal and urinary disorders Urethral pain	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Urinary retention	0.44% 1/227	0.00% 0/115	0.88% 1/113
Reproductive system and breast disorders Bartholin's cyst	0.00% 0/122	1.9% 1/53	0.00% 0/64
Reproductive system and breast disorders Breast inflammation	0.00% 0/227	0.87% 1/115	0.00% 0/113
Reproductive system and breast disorders Breast pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
Reproductive system and breast disorders Breast tenderness	0.44% 1/227	0.00% 0/115	0.00% 0/113
Reproductive system and breast disorders Dysmenorrhoea	0.82% 1/122	0.00% 0/53	1.6% 1/64
Reproductive system and breast disorders Fibrocystic breast disease	0.00% 0/227	0.87% 1/115	0.00% 0/113
Reproductive system and breast disorders Menstruation irregular	0.44% 1/227	0.00% 0/115	0.00% 0/113
Reproductive system and breast disorders Pelvic floor muscle weakness	0.82% 1/122	0.00% 0/53	0.00% 0/64
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/122	0.00% 0/53	1.6% 1/64
Reproductive system and breast disorders Uterine polyp	0.00% 0/122	1.9% 1/53	1.6% 1/64
Respiratory, thoracic and mediastinal disorders Allergic sinusitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Cough	2.6% 6/227	4.3% 5/115	3.5% 4/113
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.44% 1/227	0.87% 1/115	0.88% 1/113
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/227	0.87% 1/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.88% 2/227	3.5% 4/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/227	0.00% 0/115	0.88% 1/113
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.88% 2/227	1.7% 2/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.44% 1/227	0.87% 1/115	1.8% 2/113
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.88% 2/227	2.6% 3/115	0.88% 1/113
Respiratory, thoracic and mediastinal disorders Sinus congestion	1.3% 3/227	2.6% 3/115	2.7% 3/113
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.88% 2/227	0.87% 1/115	0.00% 0/113
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	0.00% 0/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Acne	0.00% 0/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Blister	0.88% 2/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Chronic spontaneous urticaria	0.00% 0/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Dermal cyst	0.44% 1/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Dermatitis contact	1.8% 4/227	0.00% 0/115	1.8% 2/113
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Erythema	2.6% 6/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Hyperhidrosis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Hyperkeratosis	0.44% 1/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Ingrowing Nail	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Lipohypertrophy	0.00% 0/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Onychomadesis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Pruritus	1.3% 3/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Rash	2.2% 5/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Rash erythematous	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/227	0.00% 0/115	0.88% 1/113
Skin and subcutaneous tissue disorders Scab	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Skin mass	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/227	0.87% 1/115	0.88% 1/113
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/227	0.87% 1/115	0.88% 1/113
Social circumstances Menopause	0.82% 1/122	0.00% 0/53	0.00% 0/64
Vascular disorders Aortic arteriosclerosis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Vascular disorders Hypertension	1.8% 4/227	0.87% 1/115	1.8% 2/113
Vascular disorders Hypotension	0.44% 1/227	0.00% 0/115	0.00% 0/113
Vascular disorders Varicose vein	0.00% 0/227	0.00% 0/115	0.88% 1/113
General disorders Chest pain	0.44% 1/227	0.87% 1/115	0.00% 0/113
Gastrointestinal disorders Oesophagitis	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Abscess limb	0.44% 1/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Convulsion	0.44% 1/227	0.00% 0/115	0.00% 0/113
Cardiac disorders Bradycardia	0.00% 0/227	0.87% 1/115	0.00% 0/113
Cardiac disorders Tachycardia	0.00% 0/227	0.87% 1/115	0.00% 0/113
Ear and labyrinth disorders Ear pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
Ear and labyrinth disorders Eustachian tube dysfunction	0.00% 0/227	0.87% 1/115	0.00% 0/113
Ear and labyrinth disorders Otorrhoea	0.00% 0/227	0.00% 0/115	0.88% 1/113
Endocrine disorders Hypothyroidism	0.00% 0/227	0.87% 1/115	0.88% 1/113
Eye disorders Eye haemorrhage	0.44% 1/227	0.00% 0/115	0.00% 0/113
Eye disorders Vitreous haemorrhage	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Coeliac disease	0.00% 0/227	0.87% 1/115	0.00% 0/113
Gastrointestinal disorders Gastric ulcer	0.00% 0/227	0.87% 1/115	0.00% 0/113
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/227	0.87% 1/115	0.00% 0/113
Gastrointestinal disorders Tooth impacted	0.00% 0/227	0.87% 1/115	0.00% 0/113
General disorders Hunger	0.44% 1/227	0.00% 0/115	0.00% 0/113
Hepatobiliary disorders Biliary colic	0.00% 0/227	0.87% 1/115	0.00% 0/113
Hepatobiliary disorders Cholestasis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Immune system disorders Allergy to chemicals	0.00% 0/227	0.00% 0/115	0.88% 1/113
Immune system disorders Allergy to metals	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Bronchitis viral	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Enteritis infectious	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Eye infection viral	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Fungal infection	0.00% 0/227	0.87% 1/115	0.88% 1/113
Infections and infestations Gastrointestinal infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Gastrointestinal viral infection	1.3% 3/227	0.87% 1/115	0.00% 0/113
Infections and infestations H1N1 Influenza	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Herpes zoster	0.00% 0/227	0.00% 0/115	1.8% 2/113
Infections and infestations Hordeolum	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Infectious mononucleosis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Mycobacteriuim abscessus infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Oral candidiasis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Pilonidal cyst	0.00% 0/227	0.87% 1/115	0.00% 0/113
Infections and infestations Rhinitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Staphylococcal skin infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Tonsillitis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Infections and infestations Viral upper respiratory tract infection	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Contusion	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Fall	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Fascial rupture	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Foreign body	0.44% 1/227	0.00% 0/115	0.00% 0/113
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/227	0.00% 0/115	0.88% 1/113
Injury, poisoning and procedural complications Limb injury	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Radius fracture	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Rib fracture	0.00% 0/227	0.87% 1/115	0.00% 0/113
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/227	0.87% 1/115	0.00% 0/113
Investigations Alanine aminotransferase increased	0.00% 0/227	0.00% 0/115	0.88% 1/113
Investigations Blood bilirubin increased	0.00% 0/227	0.00% 0/115	0.88% 1/113
Investigations Carotid bruit	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Abnormal loss of weight	0.00% 0/227	0.87% 1/115	0.00% 0/113
Metabolism and nutrition disorders Decreased appetite	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Hypokalaemia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Metabolism and nutrition disorders Tetany	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/227	0.87% 1/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/227	0.87% 1/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Muscular weakness	0.44% 1/227	0.00% 0/115	0.00% 0/113
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/227	0.00% 0/115	1.8% 2/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/227	0.00% 0/115	0.88% 1/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Knuckle pads	0.44% 1/227	0.00% 0/115	0.00% 0/113
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Morton's neuroma	0.44% 1/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Amnesia	0.00% 0/227	0.00% 0/115	0.88% 1/113
Nervous system disorders Cerebrovascular accident	0.44% 1/227	0.00% 0/115	0.00% 0/113
Nervous system disorders Dizziness	0.00% 0/227	0.87% 1/115	0.00% 0/113
Nervous system disorders Neuralgia	0.00% 0/227	0.87% 1/115	0.88% 1/113
Psychiatric disorders Binge eating	0.00% 0/227	0.87% 1/115	0.00% 0/113
Psychiatric disorders Panic attack	0.00% 0/227	0.87% 1/115	0.00% 0/113
Renal and urinary disorders Calculus bladder	0.44% 1/227	0.00% 0/115	0.00% 0/113
Renal and urinary disorders Cystitis noninfective	0.44% 1/227	0.00% 0/115	0.00% 0/113
Reproductive system and breast disorders Erectile dysfunction	0.44% 1/227	0.00% 0/115	0.00% 0/113
Reproductive system and breast disorders Menorrhagia	0.00% 0/227	1.7% 2/115	0.00% 0/113
Reproductive system and breast disorders Vulvovaginal pruritus	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Eczema	0.00% 0/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Scar pain	0.00% 0/227	0.87% 1/115	0.00% 0/113
Skin and subcutaneous tissue disorders Skin irritation	0.44% 1/227	0.00% 0/115	0.00% 0/113
Skin and subcutaneous tissue disorders Stasis dermatitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Surgical and medical procedures Wisdom teeth removal	0.00% 0/227	0.00% 0/115	0.88% 1/113
Immune system disorders Sarcoidosis	0.00% 0/227	0.00% 0/115	0.88% 1/113
Eye disorders Keratitis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Infections and infestations Candidiasis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Blood and lymphatic system disorders Anaemia	1.3% 3/227	0.87% 1/115	0.00% 0/113
Blood and lymphatic system disorders Iron deficiency anaemia	0.44% 1/227	0.00% 0/115	0.00% 0/113
Cardiac disorders Atrial fibrillation	0.00% 0/227	0.00% 0/115	1.8% 2/113
Cardiac disorders Coronary artery disease	0.44% 1/227	0.00% 0/115	0.88% 1/113
Cardiac disorders Palpitations	0.88% 2/227	0.00% 0/115	0.88% 1/113
Ear and labyrinth disorders Tinnitus	0.00% 0/227	0.87% 1/115	0.00% 0/113
Ear and labyrinth disorders Vertigo	0.44% 1/227	1.7% 2/115	0.88% 1/113
Endocrine disorders Goitre	0.88% 2/227	0.00% 0/115	0.00% 0/113
Endocrine disorders Hypogonadism	0.44% 1/227	0.00% 0/115	0.00% 0/113
Eye disorders Angle closure glaucoma	0.00% 0/227	0.00% 0/115	0.88% 1/113
Eye disorders Cataract	0.00% 0/227	0.87% 1/115	0.88% 1/113
Eye disorders Conjunctivitis	0.88% 2/227	0.00% 0/115	0.00% 0/113
Eye disorders Diabetic retinopathy	0.44% 1/227	0.00% 0/115	0.00% 0/113
Eye disorders Dry eye	0.44% 1/227	0.00% 0/115	0.88% 1/113
Eye disorders Eye discharge	0.00% 0/227	0.87% 1/115	0.00% 0/113
Eye disorders Macular oedema	0.00% 0/227	0.87% 1/115	0.00% 0/113
Eye disorders Retinal haemorrhage	1.3% 3/227	0.00% 0/115	0.00% 0/113
Eye disorders Vitreous floaters	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Abdominal discomfort	1.8% 4/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Abdominal distention	0.00% 0/227	0.87% 1/115	0.00% 0/113
Gastrointestinal disorders Abdominal pain	0.88% 2/227	0.87% 1/115	0.88% 1/113
Gastrointestinal disorders Abdominal pain upper	1.3% 3/227	0.00% 0/115	2.7% 3/113
Gastrointestinal disorders Colitis ulcerative	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Constipation	0.44% 1/227	0.87% 1/115	0.88% 1/113
Gastrointestinal disorders Dental caries	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Diarrhoea	2.6% 6/227	1.7% 2/115	0.00% 0/113
Gastrointestinal disorders Dyspepsia	0.00% 0/227	0.00% 0/115	0.88% 1/113
Gastrointestinal disorders Gastritis	0.44% 1/227	0.00% 0/115	0.00% 0/113
Gastrointestinal disorders Gastrooesophageal reflux disease	0.88% 2/227	1.7% 2/115	0.88% 1/113
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/227	0.00% 0/115	0.88% 1/113

Additional Information

Dimitrios Chondros, M.D., Chief Medical Officer

Halozyme Therapeutics

Phone: 858-794-8889

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. The Investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless written permission from the sponsor (Halozyme) is obtained.
Publication restrictions are in place

Restriction type: OTHER