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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)

Primary Purpose

Type 1 Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Commercial Hylenex® recombinant (hyaluronidase human injection)

Precommercial Hylenex recombinant (hyaluronidase human injection)

Insulin lispro

Insulin aspart

Insulin glulisine

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Type 1 Diabetes Mellitus, Sub Cutaneous Insulin Infusion, Rapid Acting Analog Insulin, Hylenex, Halozyme, Phase 4

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female of age 18 years or older with a history of T1DM for at least 12 months
Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory results
Fasting C-peptide <0.6 nanograms per milliliter (ng/mL)
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
Current treatment at the time of screening with insulin <300 units per day (U/day)
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.
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:

Type 2 diabetes
Known or suspected allergy to any component of any of the study drugs in this study
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
History of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure [BP] consistently >100 millimeters of mercury [mmHg]) are exclusionary
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
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
As judged by the Investigator, clinically significant findings in routine laboratory data at screening
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.
Hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator.
Current addiction to alcohol or substance abuse as determined by the Investigator.
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.
Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

Sites / Locations

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time
For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Commercial Hylenex Recombinant (Formulation 1)

Precommercial Hylenex Recombinant (Formulation 2)

Standard Rapid-Acting Insulin CSII

Arm Description

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

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

Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.

Outcomes

Primary Outcome Measures

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

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

Change From Baseline to 12 Months in HbA1c

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

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

Change From Baseline in Body Weight to Month 12

Baseline is defined as the last measurement prior to randomization.

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.

Average Carbohydrate Factor (CarbF) Values

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

Average Correction Factor (CorrF) Values

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

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.

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 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.

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.

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).

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.

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.

Mean Time to Change Infusion Site

Mean Additional Time for Hylenex Pre-administration

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

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.

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

Full Information

NCT ID

NCT01848990

First Posted

April 29, 2013

Last Updated

October 10, 2018

Sponsor

Halozyme Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT01848990

Brief Title

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)

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Halozyme Therapeutics

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

456 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Commercial Hylenex Recombinant (Formulation 1)

Arm Type

Experimental

Arm Description

Arm Title

Precommercial Hylenex Recombinant (Formulation 2)

Arm Type

Experimental

Arm Description

Arm Title

Standard Rapid-Acting Insulin CSII

Arm Type

Active Comparator

Arm Description

Participants received their regular treatment of rapid-acting CSII (for example, insulin lispro, insulin aspart, and insulin glulisine) for 6 months.

Intervention Type

Drug

Intervention Name(s)

Commercial Hylenex® recombinant (hyaluronidase human injection)

Other Intervention Name(s)

Formulation 1, Hylenex, Recombinant human hyaluronidase (rHuPH20)

Intervention Type

Drug

Intervention Name(s)

Precommercial Hylenex recombinant (hyaluronidase human injection)

Other Intervention Name(s)

Formulation 2, Hylenex, rHuPH20

Intervention Type

Drug

Intervention Name(s)

Insulin lispro

Other Intervention Name(s)

Humalog, Lispro

Intervention Type

Drug

Intervention Name(s)

Insulin aspart

Other Intervention Name(s)

Novolog, Aspart

Intervention Type

Drug

Intervention Name(s)

Insulin glulisine

Other Intervention Name(s)

Apidra, Glulisine

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Baseline; 6 Months

Title

Change From Baseline to 12 Months in HbA1c

Description

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

Time Frame

Baseline; 12 Months

Secondary Outcome Measure Information:

Title

Rates of Hypoglycemia Events (HE) to Month 6

Description

Time Frame

After Month 1 up to Month 6

Title

Rates of HEs to Month 12

Description

Time Frame

After Month 1 up to Month 12

Title

Rates of Hyperglycemia Events to Month 6

Description

Time Frame

After Month 1 up to Month 6

Title

Rates of Hyperglycemia Events to Month 12

Description

Time Frame

After Month 1 up to Month 12

Title

Mean Glucose Excursions at 6 Months

Description

Time Frame

After Month 1 up to Month 6

Title

Mean Glucose Excursions at 12 Months

Description

Time Frame

After Month 1 up to Month 12

Title

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

Description

Time Frame

After Month 1 up to Month 6

Title

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

Description

Time Frame

After Month 1 up to Month 12

Title

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

Description

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

Time Frame

Month 12

Title

Change From Baseline in Body Weight to Month 12

Description

Baseline is defined as the last measurement prior to randomization.

Time Frame

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

Title

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

Description

Time Frame

from Randomization up to Month 12

Title

Average Carbohydrate Factor (CarbF) Values

Description

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

Time Frame

Month 1 to Month 12

Title

Average Correction Factor (CorrF) Values

Description

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

Time Frame

Month 1 to Month 12

Title

Average of Bolus Times Relative to Meal Times

Description

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

Title

Average Glucose, Median Glucose, and Average Daily Standard Deviation

Description

Time Frame

Randomization to Month 12

Title

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

Description

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

Title

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

Description

Time Frame

Randomization to Month 12

Title

Change From Baseline in Weighted Impact ADDQoL Values at Month 12

Description

Time Frame

Baseline; Month 12

Title

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

Description

Time Frame

Baseline; Month 12

Title

Change From Baseline in DTSQs and DTSQc at Month 12

Description

Time Frame

Baseline; Month 12

Title

Mean Time to Change Infusion Site

Description

Time Frame

Month 12

Title

Mean Additional Time for Hylenex Pre-administration

Description

Time Frame

Month 12

Title

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

Description

Time Frame

Month 12

Title

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

Description

Time Frame

Month 12

Title

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

Description

Time Frame

Month 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female of age 18 years or older with a history of T1DM for at least 12 months Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory results Fasting C-peptide <0.6 nanograms per milliliter (ng/mL) 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 Current treatment at the time of screening with insulin <300 units per day (U/day) 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. 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: Type 2 diabetes Known or suspected allergy to any component of any of the study drugs in this study 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 History of transmural myocardial infarction, congestive heart failure and uncontrolled hypertension (diastolic blood pressure [BP] consistently >100 millimeters of mercury [mmHg]) are exclusionary 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 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 As judged by the Investigator, clinically significant findings in routine laboratory data at screening 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. Hypoglycemic unawareness of such severity as to impede the participant's ability to comply with protocol procedures, as judged by the Investigator. Current addiction to alcohol or substance abuse as determined by the Investigator. 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. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Douglas Muchmore, MD

Organizational Affiliation

Halozyme Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Concord

State/Province

California

ZIP/Postal Code

94520

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Encino

State/Province

California

ZIP/Postal Code

91436

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Escondido

State/Province

California

ZIP/Postal Code

92026

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Greenbrae

State/Province

California

ZIP/Postal Code

94904

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

San Mateo

State/Province

California

ZIP/Postal Code

94401

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Hollywood

State/Province

Florida

ZIP/Postal Code

33021

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Miami

State/Province

Florida

ZIP/Postal Code

33156

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30318

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Roswell

State/Province

Georgia

ZIP/Postal Code

30076

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Idaho Falls

State/Province

Idaho

ZIP/Postal Code

83404

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Des Moines

State/Province

Iowa

ZIP/Postal Code

50314

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67226

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40503

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Hyattsville

State/Province

Maryland

ZIP/Postal Code

20782

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Rockville

State/Province

Maryland

ZIP/Postal Code

20852

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55416

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Butte

State/Province

Montana

ZIP/Postal Code

59701

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Henderson

State/Province

Nevada

ZIP/Postal Code

89052

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89148

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

New Hyde Park

State/Province

New York

ZIP/Postal Code

11042

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Asheville

State/Province

North Carolina

ZIP/Postal Code

28803

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27713

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Morehead City

State/Province

North Carolina

ZIP/Postal Code

28557

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Portland

State/Province

Oregon

ZIP/Postal Code

97210

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Bartlett

State/Province

Tennessee

ZIP/Postal Code

38133

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37411

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Austin

State/Province

Texas

ZIP/Postal Code

78731

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Round Rock

State/Province

Texas

ZIP/Postal Code

78681

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78258

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Olympia

State/Province

Washington

ZIP/Postal Code

98502

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Renton

State/Province

Washington

ZIP/Postal Code

98057

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Seattle

State/Province

Washington

ZIP/Postal Code

98105

Country

United States

Facility Name

For additional information regarding investigative sites for this trial, call (858) 794-8889 8 AM to 5 PM Mon-Fri Pacific Standard Time

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53717

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.halozyme.com

Description

Related Info

Learn more about this trial

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)

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