HALO-117-406: A Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Function in Subjects With Type 1 Diabetes With Recombinant Human Hyaluronidase (rHuPH20)

• Sponsor: Halozyme Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03662334
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 4.8
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The goal of this study is to determine if Hylenex recombinant leads to changes in the insulin time-action profiles and glucose responses when preadministered in the setting of continuous subcutaneous insulin infusion (CSII) compared to CSII without Hylenex recombinant (sham injection).

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Drug: Rapid Acting insulin with pre-treatment of rHuPH20; Device: Sham injection	Phase 4

Detailed Description

There is a recognized need for more rapid insulin action than is available from current rapid-acting analog products. In addition, current products have inconstant absorption and action profiles over the course of infusion set life. Previous human studies of prandial insulin preparations have used co-mixtures of rHuPH20 (study drug) with insulin delivered to study participants by subcutaneous injection and have demonstrated acceleration of insulin absorption and action. CSII has been used clinically for the treatment of diabetes over the last three decades, and a previous study using a co-mixture of rHuPH20 during CSII showed that the combination resulted in a more consistent and ultrafast profile of insulin absorption and action across infusion set use as compared to rapid analog insulin alone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Double Blind, Single Center, Randomized, Cross-Over Study of Continuous Subcutaneous Insulin Infusion (CSII) Pump Functionality in Subjects With Type 1 Diabetes Comparing Pretreatment vs. No Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
• Actual Study Start Date: Oct 3, 2013
• Actual Primary Completion Date: Feb 27, 2014
• Actual Study Completion Date: Feb 27, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hylenex recombinant Comparing the preadministration of Hylenex recombinant in the setting of continuous subcutaneous insulin infusion (CSII).	Drug: Rapid Acting insulin with pre-treatment of rHuPH20; Hylenex recombinant will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.; Other Names: Humalog Hylenex
Sham Comparator: Sham Injection Comparing the preadministration of a sham injection in the setting of CSII.	Device: Sham injection; A sham injection will be administered via infusion sets and insulin pumps. These will be compatible with component tubing system attached to the insulin infusion site and will be placed in the lower abdominal area.; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours [0-6 hours]

2. Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus [0-10 hours]

   Time to reduction is reported as the maximum time it took for any participant receiving each treatment sequence to achieve a reduction in plasma glucose by 80 mg/dL. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.

3. Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp [0-12 hours]

Secondary Outcome Measures

1. Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants [up to approximately 10 hours]

2. Part 1: Mean Maximum Concentration (Cmax) [up to approximately 22 hours]

3. Part 1: Time to Achieve Maximum Concentration (Tmax) [up to approximately 22 hours]

4. Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max [up to approximately 22 hours]

5. Part 1: Time to 50% of Total AUC (AUC0-last) [up to approximately 22 hours]

6. Part 1: Fractional and Absolute AUC0-1hr [0 to 1 hour]

7. Part 1: Fractional and Absolute AUC2hr-end [2 to approximately 22 hours]

8. Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last) [up to approximately 22 hours]

9. Part 1: Mean Residence Time (MRT) [up to approximately 22 hours]

10. Part 2: Plasma Glucose Concentration Over Time [up to approximately 10 hours]

    Plasma glucose concentration over time is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.

11. Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion [up to approximately 10 hours]

    Insulin analog serum concentration is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.

12. Part 3: Plasma Glucose Concentration Over Time [up to approximately 12 hours]

13. Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion [up to approximately 12 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female participants between the ages 18 and 65 years, inclusive.

2. Females of child-bearing potential must agree to use a standard and effective means of birth control for the duration of the study. Adequate contraceptive measures include oral or injectable contraceptives, sterilization, intra-uterine device (IUD), barrier methods, or abstinence.

3. Participants with type 1 diabetes mellitus treated with insulin (multiple daily injections or continuous subcutaneous insulin infusion [CSII]) diagnosed ≥ 12 months prior to enrollment

4. Body mass index (BMI) 18.0 to 32.0 kilograms per meters squared (kg/m^2)

5. HbA1c (glycated hemoglobin A1c) ≤ 10% based on local laboratory results

6. Fasting C-peptide < 0.6 nanograms per milliliter (ng/mL)

7. Current treatment with insulin <1.2 Units per kg per day (U/kg/day)

8. Participant should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments required in this protocol

Exclusion Criteria:

1. Inability to comply with study requirements as judged by the Investigator

2. Known or suspected allergy to any component of any of the study drugs in this trial

3. A participant who has proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator

4. As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram), hepatic, neurological, renal, genitourinary, or hematological systems

5. As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure ≥ 100 millimeters of mercury [mmHg] and/or systolic blood pressure ≥ 160 mmHg after 5 minutes in the supine position)

6. History of any illness or disease that in the opinion of the Investigator might confound the results of the trial 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. Anemia with hemoglobin less than lower limits of normal at screening is specifically exclusionary

8. Use of drugs that may interfere with the interpretation of trial results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia, or drugs not permitted according to Hylenex recombinant package insert

9. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator

10. Current addiction to alcohol or substances of abuse as determined by the Investigator

11. Blood donation (> 500 mL) within the previous 8 weeks (56 days) prior to Day -1 of Treatment Period 1

12. Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, IUD, oral or injectable contraceptives, or barrier methods)

13. Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study

14. Participation in any other clinical trial and receipt of any investigational drug within 4 weeks of Day -1 of Treatment Period 1

15. Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with trial participation or evaluation of data

16. Positive for human immunodeficiency virus (HIV), Hepatitis C or Hepatitis B

17. Tobacco and nicotine use within 3 months prior to Day 1 of Treatment Period 1 or use during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Profil Institute for Clinical Research	Chula Vista	California	United States	91911

Sponsors and Collaborators

• Halozyme Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Halozyme Therapeutics

Publications

None provided.

• Responsible Party: Halozyme Therapeutics
• ClinicalTrials.gov Identifier: NCT03662334
• Other Study ID Numbers: HALO-117-406
• First Posted: Sep 7, 2018
• Last Update Posted: Feb 1, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Halozyme Therapeutics: Diabetes; Type 1 Diabetes Mellitus; Type 1 Diabetes; T1DM; Continuous Subcutaneous Insulin Infusion (CSII); CSII; Insulin pump; Insulin; rHuPH20; Hylenex; recombinant human hyaluronidase (rHuPH20); Recombinant hyaluronidase
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin, Short-Acting

Study Results

Participant Flow

Pre-assignment Detail	All three parts (Parts 1, 2, and 3) of this exploratory study were to use a cross-over design that would maximize efficiency while minimizing sample size. Only Part 2 of this study was conducted; thus, all 14 participants were enrolled in Part 2 only.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Period Title: Part 1: Treatment Period 1
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0
Period Title: Part 1: Treatment Period 1
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0
Period Title: Part 1: Treatment Period 1
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0
Period Title: Part 1: Treatment Period 1
STARTED	7	7
COMPLETED	6	7
NOT COMPLETED	1	0
Period Title: Part 1: Treatment Period 1
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0
Period Title: Part 1: Treatment Period 1
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection	Total
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.	Total of all reporting groups
Overall Participants	7	7	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.6 (8.90)	40.4 (14.84)	42.0 (11.87)
Sex: Female, Male (Count of Participants)
Female	2 28.6%	2 28.6%	4 28.6%
Male	5 71.4%	5 71.4%	10 71.4%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	7 100%	7 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Part 1: Area Under the Curve (AUC) of Glucose Infusion Rate (GIR) From 0-6 Hours
Time Frame	0-6 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

2. Primary Outcome

Title	Part 2: Time to Reduction in Plasma Glucose by 80 Milligrams Per Deciliter (mg/dL) Following CSII Bolus
Description	Time to reduction is reported as the maximum time it took for any participant receiving each treatment sequence to achieve a reduction in plasma glucose by 80 mg/dL. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
Time Frame	0-10 hours

Outcome Measure Data

Analysis Population Description

Safety Population: all randomized participants exposed to at least one dose of study drug

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	7	7
First Intervention	5.58	5.23
Second Intervention	4.63	5.32

3. Primary Outcome

Title	Part 3: Time to Achieve Plasma Glucose >90 mg/dL After Release of Hypoglycemic CSII Clamp
Time Frame	0-12 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

4. Secondary Outcome

Title	Part 1: Time-action Profile, Assessed by GIR in Euglycemic Participants
Time Frame	up to approximately 10 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

5. Secondary Outcome

Title	Part 1: Mean Maximum Concentration (Cmax)
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

6. Secondary Outcome

Title	Part 1: Time to Achieve Maximum Concentration (Tmax)
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

7. Secondary Outcome

Title	Part 1: Early Time to 50% Maximum Serum Insulin Concentration (t50%) Max
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

8. Secondary Outcome

Title	Part 1: Time to 50% of Total AUC (AUC0-last)
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

9. Secondary Outcome

Title	Part 1: Fractional and Absolute AUC0-1hr
Time Frame	0 to 1 hour

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

10. Secondary Outcome

Title	Part 1: Fractional and Absolute AUC2hr-end
Time Frame	2 to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

11. Secondary Outcome

Title	Part 1: Area Under the Curve From Time Zero to the Last Measureable Concentration (AUC0-last)
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

12. Secondary Outcome

Title	Part 1: Mean Residence Time (MRT)
Time Frame	up to approximately 22 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

13. Secondary Outcome

Title	Part 2: Plasma Glucose Concentration Over Time
Description	Plasma glucose concentration over time is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
Time Frame	up to approximately 10 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	7	7
First Intervention	299	341
Second Intervention	350	445

14. Secondary Outcome

Title	Part 2: Insulin Analog Serum Concentration as a Function of Time Following Bolus Insulin Infusion
Description	Insulin analog serum concentration is reported as the maximum concentration for any participant receiving each treatment sequence. During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 mg/dL, even after adjusting several operational parameters. The study was stopped early, prior to enrolling the planned 24 participants for Part 2. Thus, analysis for this endpoint was not conducted. Raw data (as a maximum) are reported.
Time Frame	up to approximately 10 hours

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	7	7
First Intervention	1341.8	805.1
Second Intervention	688.5	1092.6

15. Secondary Outcome

Title	Part 3: Plasma Glucose Concentration Over Time
Time Frame	up to approximately 12 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

16. Secondary Outcome

Title	Part 3: Insulin Analog Serum Concentration as a Function of Time Following Termination of Insulin Infusion
Time Frame	up to approximately 12 hours

Outcome Measure Data

Analysis Population Description

The study was stopped early, prior to enrolling the planned 24 participants. As a result, data were not collected for analysis of this outcome measure. Only Part 2 of the study was conducted.

Arm/Group Title	Hyaluronidase Human Injection/Sham Injection	Sham Injection/Hyaluronidase Human Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 2.	Participants received pretreatment of 1 mL sham injection on Day 1 of Treatment Period 1. After a 3- to 7-day washout period, participants received pretreatment of 1 mL hyaluronidase human injection on Day 1 of Treatment Period 2.
Measure Participants	0	0

Adverse Events

Time Frame	155 days
Arm/Group Title	Hyaluronidase Human Injection		Sham Injection
Arm/Group Description	Participants received pretreatment of 1 milliliter (mL) hyaluronidase human injection on Day 1 of either Treatment Period 1 or Treatment Period 2. The two periods were separated by a 3- to 7-day washout period.		Participants received pretreatment of 1 mL sham injection on Day 1 of either Treatment Period 1 or Treatment Period 2. The two periods were separated by a 3- to 7-day washout period.
All Cause Mortality
	Hyaluronidase Human Injection		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Hyaluronidase Human Injection		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Hyaluronidase Human Injection		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/14 (28.6%)		2/14 (14.3%)
Gastrointestinal disorders
Abdominal Pain Upper	1/14 (7.1%)		0/14 (0%)
General disorders
Injection Site Pain	2/14 (14.3%)		0/14 (0%)
Injection Site Haematoma	1/14 (7.1%)		0/14 (0%)
Pyrexia	0/14 (0%)		1/14 (7.1%)
Infections and infestations
Upper Respiratory Tract Infection	0/14 (0%)		1/14 (7.1%)
Metabolism and nutrition disorders
Hyperglycaemia	1/14 (7.1%)		0/14 (0%)

Limitations/Caveats

During the course of the study, it became difficult to establish a stable hyperglycemic plateau with a target glucose level of 220 milligrams per deciliter. The study was stopped early, prior to enrolling the planned 24 participants for Part 2.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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