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)

CONtinuous Subcutaneous Insulin Infusion STudy ENrolling Type 1 (CONSISTENT 1): Evaluation of Metabolic Outcomes and Safety of Hylenex Recombinant (Hyaluronidase Human Injection) Used as a Preadministration Infusion Site Treatment in Subjects With Type 1 Diabetes (T1DM) Using Continuous Subcutaneous Insulin Infusion (CSII)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01848990

Enrollment

456

Registered

2013-05-08

Start date

2013-03-31

Completion date

2014-09-30

Last updated

2018-11-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus, Sub Cutaneous Insulin Infusion, Rapid Acting Analog Insulin, Hylenex, Halozyme, Phase 4

Brief summary

The primary objectives of this study are to compare the difference in glycosylated hemoglobin (HbA1c) from baseline to Month 6 using Hylenex recombinant preadministration in continuous subcutaneous insulin infusion (CSII) versus standard CSII and to evaluate the safety of Hylenex recombinant preadministration, including local tolerability, adverse events, and hypo- and hyperglycemia rates.

Detailed description

This Phase 4 study is designed to demonstrate noninferiority of pretreatment with Hylenex recombinant in the CSII setting to rapid-acting analog insulin alone with respect to glycemic control as assessed by changes in HbA1c in participants with Type 1 diabetes mellitus. Total duration of study treatment is 24 months. However, according to the study design, the primary outcome measure is to be assessed at 6 months and an interim analysis is to be completed at 6 months for the secondary outcome measures and adverse events. Therefore, data reported in this clinical trials record is for the 6-month interim analysis.

Interventions

DRUGCommercial Hylenex® recombinant (hyaluronidase human injection)

DRUGPrecommercial Hylenex recombinant (hyaluronidase human injection)

DRUGInsulin lispro

DRUGInsulin aspart

DRUGInsulin glulisine

Study design

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or female of age 18 years or older with a history of T1DM for at least 12 months 2. Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory results 3. Fasting C-peptide \<0.6 nanograms per milliliter (ng/mL) 4. Current use of an insulin pump compatible with available tubing for Hylenex recombinant infusion and use of an infusion set compatible with the tubing available or willingness to switch to an infusion set compatible with tubing available for infusion of Hylenex recombinant 5. Current treatment at the time of screening with insulin \<300 units per day (U/day) 6. Participants who routinely use continuous glucose monitoring (CGM) (defined as average CGM use 5 or more days per week over the preceding 3 months) and those who do not routinely used CGM are both eligible for inclusion in the study. Intermittent use of CGM is also acceptable but will not be a criterion use for stratified randomization. 7. Participants should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug infusions and assessments required in this protocol.

Exclusion criteria

1. Type 2 diabetes 2. Known or suspected allergy to any component of any of the study drugs in this study 3. Severe proliferative retinopathy or maculopathy, and/or gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator 4. History of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure \[BP\] consistently \>100 millimeters of mercury \[mmHg\]) are exclusionary 5. As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including history of stroke, history of arrhythmia, or conduction delays on electrocardiogram \[ECG\]), hepatic, neurological, renal, genitourinary, pulmonary, or hematological systems of such severity as to impede the participant's ability to comply with protocol procedures 6. History of any illness or disease that in the opinion of the Investigator might confound the results of the study or pose additional risk in administering the study drugs to the participant 7. As judged by the Investigator, clinically significant findings in routine laboratory data at screening 8. Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with hyaluronidase action, insulin action, glucose utilization, or recovery from hypoglycemia (including systemic pharmacologic corticosteroid). Use of pramlintide or a glucagon-like peptide \[GLP\]-1 receptor agonist is not exclusionary but participants using these agents will be subjected to stratified randomization. Use of aspirin (acetylsalicylic acid \[ASA\]) up to 325 milligrams (mg)/day is not exclusionary but should be noted for analysis. 9. Hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator. 10. Current addiction to alcohol or substance abuse as determined by the Investigator. 11. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[IUD\], oral or injectable contraceptives, and/or barrier methods). Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study. 12. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Rates of HEs to Month 12	After Month 1 up to Month 12	Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter \[mg/dL\] and \<56 mg/dL) were based on measurements after 1 month up to 12 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.
Rates of Hyperglycemia Events to Month 6	After Month 1 up to Month 6	Overall rates of hyperglycemia (defined as blood glucose \>240 mg/dL and \>300 mg/dL) were based on measurements after 1 month up to 6 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.
Rates of Hyperglycemia Events to Month 12	After Month 1 up to Month 12	Overall rates of hyperglycemia (defined as blood glucose \>240 mg/dL and \>300 mg/dL) were based on measurements after 1 month up to 12 months. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.
Mean Glucose Excursions at 6 Months	After Month 1 up to Month 6	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.
Mean Glucose Excursions at 12 Months	After Month 1 up to Month 12	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.
Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months	After Month 1 up to Month 6	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.
Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months	After Month 1 up to Month 12	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.
Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12	Month 12	The number of participants achieving HbA1c goals of \<7% and ≤6.5% was calculated.
Change From Baseline in Body Weight to Month 12	Baseline; Week 2; Months 1, 2, 3, 4, 6, 9, and 12	Baseline is defined as the last measurement prior to randomization.
Average of Daily Insulin Doses (Bolus, Basal, and Total)	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.
Average Carbohydrate Factor (CarbF) Values	Month 1 to Month 12	CarbF is calculated as 2.6 \* weight (pounds) / total daily dose of insulin (grams per unit).
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	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.
Average of Bolus Times Relative to Meal Times	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.
Average Glucose, Median Glucose, and Average Daily Standard Deviation	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.
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	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.
Change From Baseline in Weighted Impact ADDQoL Values at Month 12	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).
Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12	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.
Change From Baseline in DTSQs and DTSQc at Month 12	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.
Mean Time to Change Infusion Site	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.
Mean Additional Time for Hylenex Pre-administration	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.
Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	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.
Number of Participants With the Indicated Responses to the Device Handling Questions	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.
Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action	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.
Average Correction Factor (CorrF) Values	Month 1 to Month 12	CorrF is calculated as 1960 / total daily dose of insulin (milligrams/\[deciliter\*unit\]).
Rates of Hypoglycemia Events (HE) to Month 6	After Month 1 up to Month 6	Overall rates of hypoglycemia (defined as blood glucose ≤70 milligrams per deciliter \[mg/dL\] and \<56 mg/dL) were based on measurements after 1 month up to 6 months. A severe HE was classified as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. A nocturnal HE was classified as an event with a blood glucose of ≤70 mg/dL with start time between 2300 and 0600, inclusive. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Comparisons were made by pooling all of the rHuPH20 pretreatment participants (including both Formulations 1 and 2) and comparing against the standard CSII treatment arm. Formulation 1 versus Formulation 2 was compared as a supportive analysis.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Commercial Hylenex Recombinant (Formulation 1) Hylenex Formulation 1: For 12 months, participants received their regular treatment of rapid-acting continuous CSII (for example, insulin lispro, insulin aspart, and insulin glulisine). Additionally, during this 12-month treatment period, the participants received a pretreatment dose of the commercial form of Hylenex recombinant, delivered at 150 U through their insulin infusion cannula each time they changed infusion sets (every 2 to 3 days).	227
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).	115
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.	113
Total	455

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	6	2	0
Overall Study	Death	1	0	1
Overall Study	Lost to Follow-up	6	2	2
Overall Study	Non Compliance	1	0	0
Overall Study	Other	1	4	2
Overall Study	Physician Decision	1	1	0
Overall Study	Protocol Violation	1	1	0
Overall Study	Withdrawal by Subject	29	10	11

Baseline characteristics

Characteristic	Commercial Hylenex Recombinant (Formulation 1)	Precommercial Hylenex Recombinant (Formulation 2)	Standard Rapid-Acting Insulin CSII	Total
Age, Continuous	47.5 years STANDARD_DEVIATION 12.9	45.9 years STANDARD_DEVIATION 13.14	49.7 years STANDARD_DEVIATION 14.73	47.6 years STANDARD_DEVIATION 13.47
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants	7 Participants	5 Participants	22 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	217 Participants	108 Participants	108 Participants	433 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Asian	3 participants	0 participants	2 participants	5 participants
Race/Ethnicity, Customized Asian Indian	0 participants	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Black or African American	8 participants	3 participants	2 participants	13 participants
Race/Ethnicity, Customized White	216 participants	112 participants	107 participants	435 participants
Region of Enrollment United States	227 participants	115 participants	113 participants	455 participants
Sex: Female, Male Female	122 Participants	53 Participants	64 Participants	239 Participants
Sex: Female, Male Male	105 Participants	62 Participants	49 Participants	216 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	174 / 227	84 / 115	76 / 113
serious Total, serious adverse events	11 / 227	10 / 115	13 / 113

Outcome results

Primary

Change From Baseline to 12 Months in HbA1c

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

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline to 12 Months in HbA1c	-0.13 percentage of HbA1c	Standard Deviation 0.59
Standard Rapid-Acting Insulin CSII	Change From Baseline to 12 Months in HbA1c	-0.26 percentage of HbA1c	Standard Deviation 0.718

Comparison: Sample size calculated based on approximately 400 Pt being enrolled. No more than 10% dropout rate at 6 months allowed at least 270 Hylenex and 90 standard CSII Pt to reach primary metabolic endpoint evaluation. Assuming HbA1c standard deviation of 0.7% and population difference of 0% between treatments, Pt reaching primary efficacy endpoint would provide \>90% power to demonstrate HbA1c noninferiority at margin of 0.4% using confidence bound from 2-tailed 95% confidence interval.p-value: 0.071195% CI: [-0.01, 0.28]ANOVA

Primary

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

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

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)	-0.14 percentage of HbA1c	Standard Deviation 0.521
Standard Rapid-Acting Insulin CSII	Change From Baseline to 6 Months in Glycosylated Hemoglobin (HbA1c)	-0.18 percentage of HbA1c	Standard Deviation 0.687

Comparison: Sample size calculated based on approximately 400 participants (Pt) being enrolled. No more than 10% dropout rate at 6 months allowed at least 270 Hylenex and 90 standard CSII Pt to reach primary metabolic endpoint evaluation. Assuming HbA1c standard deviation of 0.7% and population difference of 0% between treatments, Pt reaching primary efficacy endpoint would provide \>90% power to demonstrate HbA1c noninferiority at margin of 0.4% using confidence bound from 2-tailed 95% confidence interval.p-value: 0.451695% CI: [-0.08, 0.18]ANOVA

Secondary

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

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

Time frame: Randomization to 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	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
Hylenex Recombinant	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 1232.6
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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
Standard Rapid-Acting Insulin CSII	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	43089.0 mg*minutes/deciliter	Standard Error 3033.35
Standard Rapid-Acting Insulin CSII	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	163.2 mg*minutes/deciliter	Standard Error 35.45
Standard Rapid-Acting Insulin CSII	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	771.7 mg*minutes/deciliter	Standard Error 126.69
Standard Rapid-Acting Insulin CSII	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	42317.2 mg*minutes/deciliter	Standard Error 3061.24
Standard Rapid-Acting Insulin CSII	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	20411.2 mg*minutes/deciliter	Standard Error 2012.83

p-value: 0.421695% CI: [-115.9, 48.9]ANOVA

p-value: 0.569795% CI: [-379.2, 209.8]ANOVA

p-value: 0.924195% CI: [-6772.3, 7458.2]ANOVA

p-value: 0.923295% CI: [-54.2, 59.8]ANOVA

p-value: 0.942395% CI: [-6792.2, 7308.7]ANOVA

Secondary

Average Carbohydrate Factor (CarbF) Values

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

Time frame: Month 1 to Month 12

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Average Carbohydrate Factor (CarbF) Values	11.1 grams per unit	Standard Error 0.26
Standard Rapid-Acting Insulin CSII	Average Carbohydrate Factor (CarbF) Values	11.0 grams per unit	Standard Error 0.46

p-value: 0.877895% CI: [-1, 1.1]ANOVA

Secondary

Average Correction Factor (CorrF) Values

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

Time frame: Month 1 to Month 12

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Average Correction Factor (CorrF) Values	43.2 milligrams/(deciliter*unit)	Standard Error 1.06
Standard Rapid-Acting Insulin CSII	Average Correction Factor (CorrF) Values	45.3 milligrams/(deciliter*unit)	Standard Error 1.83

p-value: 0.323395% CI: [-6.3, 2.1]ANOVA

Secondary

Average Glucose, Median Glucose, and Average Daily Standard Deviation

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

Time frame: Randomization to Month 12

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Average glucose	152.9 milliliters per deciliter	Standard Error 1.79
Hylenex Recombinant	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Median glucose	145.2 milliliters per deciliter	Standard Error 1.8
Hylenex Recombinant	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Average daily standard deviation	48.9 milliliters per deciliter	Standard Error 0.85
Standard Rapid-Acting Insulin CSII	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Average glucose	151.9 milliliters per deciliter	Standard Error 2.93
Standard Rapid-Acting Insulin CSII	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Median glucose	143.4 milliliters per deciliter	Standard Error 2.94
Standard Rapid-Acting Insulin CSII	Average Glucose, Median Glucose, and Average Daily Standard Deviation	Average daily standard deviation	49.7 milliliters per deciliter	Standard Error 1.39

p-value: 0.770895% CI: [-5.8, 7.8]ANOVA

p-value: 0.605895% CI: [-5, 8.6]ANOVA

p-value: 0.657195% CI: [-4, 2.5]ANOVA

Secondary

Average of Bolus Times Relative to Meal Times

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

Time frame: Month 1 to Month 12

Arm	Measure	Group	Value (MEAN)	Dispersion
Hylenex Recombinant	Average of Bolus Times Relative to Meal Times	Breakfast	-2.3 minutes	Standard Deviation 8.17
Hylenex Recombinant	Average of Bolus Times Relative to Meal Times	Lunch	-1.8 minutes	Standard Deviation 6.75
Hylenex Recombinant	Average of Bolus Times Relative to Meal Times	Dinner	-1.7 minutes	Standard Deviation 7.48
Hylenex Recombinant	Average of Bolus Times Relative to Meal Times	Overall	-1.9 minutes	Standard Deviation 6.51
Standard Rapid-Acting Insulin CSII	Average of Bolus Times Relative to Meal Times	Overall	-2.4 minutes	Standard Deviation 7.86
Standard Rapid-Acting Insulin CSII	Average of Bolus Times Relative to Meal Times	Breakfast	-3.9 minutes	Standard Deviation 7.83
Standard Rapid-Acting Insulin CSII	Average of Bolus Times Relative to Meal Times	Dinner	-1.7 minutes	Standard Deviation 9.19
Standard Rapid-Acting Insulin CSII	Average of Bolus Times Relative to Meal Times	Lunch	-1.6 minutes	Standard Deviation 8.61

Secondary

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

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

Time frame: from Randomization up to Month 12

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily bolus dose	21.9 International units	Standard Error 0.78
Hylenex Recombinant	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily basal dose	28.0 International units	Standard Error 0.73
Hylenex Recombinant	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily total dose	49.9 International units	Standard Error 1.32
Standard Rapid-Acting Insulin CSII	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily bolus dose	22.9 International units	Standard Error 1.33
Standard Rapid-Acting Insulin CSII	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily basal dose	25.7 International units	Standard Error 1.26
Standard Rapid-Acting Insulin CSII	Average of Daily Insulin Doses (Bolus, Basal, and Total)	Daily total dose	48.5 International units	Standard Error 2.27

p-value: 0.494895% CI: [-4.1, 2]ANOVA

p-value: 0.109995% CI: [-0.5, 5.2]ANOVA

p-value: 0.58395% CI: [-3.7, 6.6]ANOVA

Secondary

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

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

Time frame: Baseline; Month 12

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12	0.0 score on a scale	Standard Error 0.07
Standard Rapid-Acting Insulin CSII	Change From Baseline in Average Weighted Impact ADDQoL Values at Month 12	0.0 score on a scale	Standard Error 0.12

p-value: 0.990195% CI: [-0.3, 0.3]ANOVA

Secondary

Change From Baseline in Body Weight to Month 12

Baseline is defined as the last measurement prior to randomization.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Week 2	-0.10 kilograms	Standard Deviation 1.272
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 1	-0.11 kilograms	Standard Deviation 1.583
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 2	-0.03 kilograms	Standard Deviation 2.002
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 3	0.16 kilograms	Standard Deviation 2.562
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 4	0.04 kilograms	Standard Deviation 2.68
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 6	0.60 kilograms	Standard Deviation 3.035
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 9	0.91 kilograms	Standard Deviation 3.355
Hylenex Recombinant	Change From Baseline in Body Weight to Month 12	Month 12	0.61 kilograms	Standard Deviation 3.796
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 12	0.48 kilograms	Standard Deviation 4.078
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Week 2	0.19 kilograms	Standard Deviation 1.257
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 4	0.37 kilograms	Standard Deviation 2.23
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 1	0.20 kilograms	Standard Deviation 1.696
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 9	0.92 kilograms	Standard Deviation 3.033
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 2	0.48 kilograms	Standard Deviation 1.672
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 6	0.83 kilograms	Standard Deviation 2.287
Standard Rapid-Acting Insulin CSII	Change From Baseline in Body Weight to Month 12	Month 3	0.37 kilograms	Standard Deviation 1.858

p-value: 0.773595% CI: [-0.76, 1.03]ANOVA

Secondary

Change From Baseline in DTSQs and DTSQc at Month 12

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

Time frame: Baseline; Month 12

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline in DTSQs and DTSQc at Month 12	DTSQs	0.0 score on a scale	Standard Error 0.32
Hylenex Recombinant	Change From Baseline in DTSQs and DTSQc at Month 12	DTSQc	9.4 score on a scale	Standard Error 0.4
Standard Rapid-Acting Insulin CSII	Change From Baseline in DTSQs and DTSQc at Month 12	DTSQs	0.0 score on a scale	Standard Error 0.53
Standard Rapid-Acting Insulin CSII	Change From Baseline in DTSQs and DTSQc at Month 12	DTSQc	9.4 score on a scale	Standard Error 0.68

p-value: 0.908195% CI: [-1.1, 1.3]ANOVA

p-value: 0.98495% CI: [-1.5, 1.6]ANOVA

Secondary

Change From Baseline in Weighted Impact ADDQoL Values at Month 12

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

Time frame: Baseline; Month 12

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Family life	0.2 score on a scale	Standard Error 0.14
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Self-confidence	0.0 score on a scale	Standard Error 0.12
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Vacations	0.0 score on a scale	Standard Error 0.15
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Motivation	0.0 score on a scale	Standard Error 0.14
Hylenex Recombinant	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
Hylenex Recombinant	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 0.1
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Close personal relationship	0.1 score on a scale	Standard Error 0.16
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Financial situation	0.1 score on a scale	Standard Error 0.14
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Do physically	-0.1 score on a scale	Standard Error 0.14
Hylenex Recombinant	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
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Sex life	0.0 score on a scale	Standard Error 0.14
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Depend on others	-0.1 score on a scale	Standard Error 0.17
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Work life	-0.1 score on a scale	Standard Error 0.15
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Freedom to eat	0.0 score on a scale	Standard Error 0.15
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Physical appearance	0.1 score on a scale	Standard Error 0.11
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Freedom to drink	-0.2 score on a scale	Standard Error 0.14
Hylenex Recombinant	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Leisure activities	-0.2 score on a scale	Standard Error 0.14
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Freedom to drink	-0.3 score on a scale	Standard Error 0.23
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Leisure activities	0.0 score on a scale	Standard Error 0.24
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Work life	0.0 score on a scale	Standard Error 0.27
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Local or long distance travel	-0.2 score on a scale	Standard Error 0.25
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Vacations	0.2 score on a scale	Standard Error 0.25
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Do physically	-0.2 score on a scale	Standard Error 0.23
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Family life	0.1 score on a scale	Standard Error 0.23
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Friendships and social life	0.1 score on a scale	Standard Error 0.22
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Close personal relationship	0.1 score on a scale	Standard Error 0.27
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Sex life	-0.3 score on a scale	Standard Error 0.24
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Physical appearance	-0.2 score on a scale	Standard Error 0.19
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Self-confidence	-0.1 score on a scale	Standard Error 0.21
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Motivation	0.3 score on a scale	Standard Error 0.24
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	The way people in general react	-0.1 score on a scale	Standard Error 0.17
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Feelings about the future	0.3 score on a scale	Standard Error 0.26
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Financial situation	0.0 score on a scale	Standard Error 0.23
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Living situation and conditions	-0.1 score on a scale	Standard Error 0.22
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Depend on others	0.4 score on a scale	Standard Error 0.28
Standard Rapid-Acting Insulin CSII	Change From Baseline in Weighted Impact ADDQoL Values at Month 12	Freedom to eat	-0.3 score on a scale	Standard Error 0.25

p-value: 0.524695% CI: [-0.7, 0.4]ANOVA

p-value: 0.63895% CI: [-0.8, 0.5]ANOVA

p-value: 0.571995% CI: [-0.7, 0.4]ANOVA

p-value: 0.405295% CI: [-0.8, 0.3]ANOVA

p-value: 0.72495% CI: [-0.4, 0.6]ANOVA

p-value: 0.687695% CI: [-0.4, 0.6]ANOVA

p-value: 0.647895% CI: [-0.4, 0.6]ANOVA

p-value: 0.974495% CI: [-0.6, 0.6]ANOVA

p-value: 0.317795% CI: [-0.3, 0.8]ANOVA

p-value: 0.208795% CI: [-0.2, 0.7]ANOVA

p-value: 0.790795% CI: [-0.4, 0.5]ANOVA

p-value: 0.344495% CI: [-0.8, 0.3]ANOVA

p-value: 0.217595% CI: [-0.1, 0.6]ANOVA

p-value: 0.206295% CI: [-1, 0.2]ANOVA

p-value: 0.876295% CI: [-0.5, 0.6]ANOVA

p-value: 0.8995% CI: [-0.5, 0.5]ANOVA

p-value: 0.136795% CI: [-1.1, 0.2]ANOVA

p-value: 0.314495% CI: [-0.3, 0.9]ANOVA

p-value: 0.686995% CI: [-0.4, 0.6]ANOVA

Secondary

Mean Additional Time for Hylenex Pre-administration

Time frame: Month 12

Arm	Measure	Value (MEAN)	Dispersion
Hylenex Recombinant	Mean Additional Time for Hylenex Pre-administration	2.9 minutes	Standard Deviation 3.96
Standard Rapid-Acting Insulin CSII	Mean Additional Time for Hylenex Pre-administration	3.8 minutes	Standard Deviation 2.84

Secondary

Mean Glucose Excursions at 12 Months

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

Time frame: After Month 1 up to Month 12

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Mean Glucose Excursions at 12 Months	Breakfast	20.1 milligrams per deciliter (mg/dL)	Standard Error 2.36
Hylenex Recombinant	Mean Glucose Excursions at 12 Months	Lunch	22.4 milligrams per deciliter (mg/dL)	Standard Error 2.17
Hylenex Recombinant	Mean Glucose Excursions at 12 Months	Dinner	12.7 milligrams per deciliter (mg/dL)	Standard Error 2.08
Hylenex Recombinant	Mean Glucose Excursions at 12 Months	Overall	17.1 milligrams per deciliter (mg/dL)	Standard Error 1.49
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 12 Months	Overall	19.7 milligrams per deciliter (mg/dL)	Standard Error 2.65
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 12 Months	Breakfast	24.9 milligrams per deciliter (mg/dL)	Standard Error 4.21
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 12 Months	Dinner	13.8 milligrams per deciliter (mg/dL)	Standard Error 3.69
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 12 Months	Lunch	21.0 milligrams per deciliter (mg/dL)	Standard Error 3.89

p-value: 0.323995% CI: [-14.3, 4.7]ANOVA

p-value: 0.75495% CI: [-7.4, 10.2]ANOVA

p-value: 0.790495% CI: [-9.5, 7.2]ANOVA

p-value: 0.401695% CI: [-8.5, 3.4]ANOVA

Secondary

Mean Glucose Excursions at 6 Months

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

Time frame: After Month 1 up to Month 6

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Mean Glucose Excursions at 6 Months	Breakfast	17.3 milligrams per deciliter (mg/dL)	Standard Error 2.77
Hylenex Recombinant	Mean Glucose Excursions at 6 Months	Lunch	22.2 milligrams per deciliter (mg/dL)	Standard Error 2.67
Hylenex Recombinant	Mean Glucose Excursions at 6 Months	Dinner	12.6 milligrams per deciliter (mg/dL)	Standard Error 2.45
Hylenex Recombinant	Mean Glucose Excursions at 6 Months	Overall	17.1 milligrams per deciliter (mg/dL)	Standard Error 1.7
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 6 Months	Overall	16.9 milligrams per deciliter (mg/dL)	Standard Error 2.91
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 6 Months	Breakfast	20.7 milligrams per deciliter (mg/dL)	Standard Error 4.76
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 6 Months	Dinner	12.5 milligrams per deciliter (mg/dL)	Standard Error 4.18
Standard Rapid-Acting Insulin CSII	Mean Glucose Excursions at 6 Months	Lunch	17.9 milligrams per deciliter (mg/dL)	Standard Error 4.58

p-value: 0.539495% CI: [-14.2, 7.5]ANOVA

p-value: 0.415195% CI: [-6.1, 14.8]ANOVA

p-value: 0.99395% CI: [-9.5, 9.6]ANOVA

p-value: 0.94195% CI: [-6.4, 6.9]ANOVA

Secondary

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

Time frame: Month 12

Arm	Measure	Value (MEAN)	Dispersion
Hylenex Recombinant	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
Standard Rapid-Acting Insulin CSII	Mean Times Per Week Participants Said They Were Eating to Avoid Going Low Due to Late Insulin Action	2.5 occurrences per week	Standard Deviation 2.37

Secondary

Mean Time to Change Infusion Site

Time frame: Month 12

Arm	Measure	Value (MEAN)	Dispersion
Hylenex Recombinant	Mean Time to Change Infusion Site	5.7 minutes	Standard Deviation 4.45
Standard Rapid-Acting Insulin CSII	Mean Time to Change Infusion Site	4.7 minutes	Standard Deviation 3.68

Secondary

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

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

Time frame: Month 12

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Hylenex Recombinant	Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12	HbA1c <7.0%	61 Participants
Hylenex Recombinant	Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12	HbA1c ≤6.5%	18 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12	HbA1c <7.0%	21 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants Achieving HbA1c <7.0% and HbA1c ≤6.5% at Month 12	HbA1c ≤6.5%	6 Participants

p-value: 0.8955Chi-squared

p-value: 0.8926Chi-squared

Secondary

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

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

Time frame: Month 12

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Completely disagree	5 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Disagree	25 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Agree	110 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Completely disagree	3 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Completely agree	31 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Completely agree	36 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Disagree	59 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Agree	165 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Agree	146 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Neither agree or disagree	34 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Neither agree or disagree	97 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Disagree	38 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Neither agree or disagree	71 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Completely disagree	3 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Completely agree	5 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Completely disagree	2 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Completely agree	0 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Agree	28 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Neither agree or disagree	44 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Disagree	22 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 1	Completely disagree	3 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Completely agree	8 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Agree	48 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Neither agree or disagree	28 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Disagree	12 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 2	Completely disagree	1 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Completely agree	14 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Agree	39 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Neither agree or disagree	22 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Device Handling Questions	Question 3	Disagree	20 Participants

Secondary

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

Time frame: Month 12

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Very easy	143 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Easy	130 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Difficult	3 Participants
Hylenex Recombinant	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Very difficult	0 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Very difficult	1 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Very easy	49 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Difficult	1 Participants
Standard Rapid-Acting Insulin CSII	Number of Participants With the Indicated Responses to the Question Regarding the Difficulty of Infusion Site Change	Easy	46 Participants

Secondary

Rates of HEs to Month 12

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

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Hylenex Recombinant	Rates of HEs to Month 12	<56 mg/dL	2.6792 events per participant per month
Hylenex Recombinant	Rates of HEs to Month 12	≤70 mg/dL	11.3803 events per participant per month
Hylenex Recombinant	Rates of HEs to Month 12	Nocturnal HEs	1.6754 events per participant per month
Hylenex Recombinant	Rates of HEs to Month 12	Severe HEs	0.0091 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of HEs to Month 12	Severe HEs	0.0085 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of HEs to Month 12	<56 mg/dL	3.3022 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of HEs to Month 12	Nocturnal HEs	1.9203 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of HEs to Month 12	≤70 mg/dL	12.3591 events per participant per month

p-value: 0.0456negative binomial model

p-value: 0.2322negative binomial model

p-value: 0.1365negative binomial model

p-value: 0.8909negative binomial model

Secondary

Rates of Hyperglycemia Events to Month 12

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

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Hylenex Recombinant	Rates of Hyperglycemia Events to Month 12	>240 mg/dL	18.9784 events per participant per month
Hylenex Recombinant	Rates of Hyperglycemia Events to Month 12	>300 mg/dL	7.1138 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hyperglycemia Events to Month 12	>240 mg/dL	18.2785 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hyperglycemia Events to Month 12	>300 mg/dL	6.8900 events per participant per month

p-value: 0.5414negative binomial model

p-value: 0.711negative binomial model

Secondary

Rates of Hyperglycemia Events to Month 6

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

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Hylenex Recombinant	Rates of Hyperglycemia Events to Month 6	>240 mg/dL	18.0422 events per participant per month
Hylenex Recombinant	Rates of Hyperglycemia Events to Month 6	>300 mg/dL	6.4768 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hyperglycemia Events to Month 6	>240 mg/dL	18.4696 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hyperglycemia Events to Month 6	>300 mg/dL	6.8155 events per participant per month

p-value: 0.7292negative binomial model

p-value: 0.5895negative binomial model

Secondary

Rates of Hypoglycemia Events (HE) to Month 6

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

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Hylenex Recombinant	Rates of Hypoglycemia Events (HE) to Month 6	<56 mg/dL	2.9103 events per participant per month
Hylenex Recombinant	Rates of Hypoglycemia Events (HE) to Month 6	≤70 mg/dL	11.6219 events per participant per month
Hylenex Recombinant	Rates of Hypoglycemia Events (HE) to Month 6	Nocturnal HEs	1.6224 events per participant per month
Hylenex Recombinant	Rates of Hypoglycemia Events (HE) to Month 6	Severe HEs	0.0055 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hypoglycemia Events (HE) to Month 6	Severe HEs	0.0160 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hypoglycemia Events (HE) to Month 6	<56 mg/dL	4.1970 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hypoglycemia Events (HE) to Month 6	Nocturnal HEs	2.0727 events per participant per month
Standard Rapid-Acting Insulin CSII	Rates of Hypoglycemia Events (HE) to Month 6	≤70 mg/dL	14.7112 events per participant per month

p-value: 0.0105negative binomial model

p-value: 0.013negative binomial model

p-value: 0.0511negative binomial model

p-value: 0.1176negative binomial model

Secondary

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

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

Time frame: After Month 1 up to Month 12

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months	72.9 mg/dL	Standard Error 1.04
Standard Rapid-Acting Insulin CSII	Standard Deviation of Self-Monitoring Blood Glucose Values at 12 Months	72.4 mg/dL	Standard Error 1.85

p-value: 0.804995% CI: [-3.7, 4.7]ANOVA

Secondary

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

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

Time frame: After Month 1 up to Month 6

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months	70.9 mg/dL	Standard Error 1.09
Standard Rapid-Acting Insulin CSII	Standard Deviation of Self-Monitoring Blood Glucose Values at 6 Months	72.2 mg/dL	Standard Error 1.86

p-value: 0.52695% CI: [-5.6, 2.9]ANOVA

Secondary

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

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

Time frame: Randomization to Month 12

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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
Hylenex Recombinant	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 2.4
Standard Rapid-Acting Insulin CSII	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	801.0 minutes	Standard Error 24.07
Standard Rapid-Acting Insulin CSII	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	20.3 minutes	Standard Error 3.91
Standard Rapid-Acting Insulin CSII	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	68.5 minutes	Standard Error 8.77
Standard Rapid-Acting Insulin CSII	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	1351.9 minutes	Standard Error 9.18
Standard Rapid-Acting Insulin CSII	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	683.7 minutes	Standard Error 27.74
Standard Rapid-Acting Insulin CSII	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	732.5 minutes	Standard Error 27.8
Standard Rapid-Acting Insulin CSII	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	461.7 minutes	Standard Error 24.54

p-value: 0.625295% CI: [-11.3, 6.9]ANOVA

p-value: 0.592995% CI: [-25.9, 14.9]ANOVA

p-value: 0.520795% CI: [-14.4, 28.3]ANOVA

p-value: 0.475495% CI: [-87.8, 41.2]ANOVA

p-value: 0.464495% CI: [-40.7, 88.6]ANOVA

p-value: 0.923295% CI: [-54.2, 59.8]ANOVA

p-value: 0.515195% CI: [-37.5, 74.4]ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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)

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline to 12 Months in HbA1c

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

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

Average Carbohydrate Factor (CarbF) Values

Average Correction Factor (CorrF) Values

Average Glucose, Median Glucose, and Average Daily Standard Deviation

Average of Bolus Times Relative to Meal Times

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

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

Change From Baseline in Body Weight to Month 12

Change From Baseline in DTSQs and DTSQc at Month 12

Change From Baseline in Weighted Impact ADDQoL Values at Month 12

Mean Additional Time for Hylenex Pre-administration

Mean Glucose Excursions at 12 Months

Mean Glucose Excursions at 6 Months

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

Mean Time to Change Infusion Site

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

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

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

Rates of HEs to Month 12

Rates of Hyperglycemia Events to Month 12

Rates of Hyperglycemia Events to Month 6

Rates of Hypoglycemia Events (HE) to Month 6

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

Standard Deviation of Self-Monitoring Blood Glucose Values at 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