Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Sham Injection

Recombinant human hyaluronidase PH20

Insulin aspart

Insulin lispro

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Type 1 Diabetes, Continuous Subcutaneous Insulin Infusion (CSII)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males or females of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
Fasting connecting peptide of insulin (C-peptide) <0.6 nanograms per milliliter (ng/mL).
Current treatment with insulin <90 units per day (U/d).
Current use of rapid acting insulin analog.
Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
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 the study protocol.

Exclusion Criteria:

Known or suspected allergy to any component of any of the study drugs in this study.
Previous enrollment in this study.
Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (for example, coumadin or heparin) will be excluded.
Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
Current addiction to alcohol or substances of abuse as determined by the Investigator.
Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of the Screening Visit(s) in this study.
Pregnancy, breastfeeding, 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, or barrier methods).
Symptomatic gastroparesis.
Receipt of any investigational drug within 4 weeks of Study Day 1.

Sites / Locations

Profil Institute for Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Insulin (Aspart or Lispro)-Sham

Insulin (Aspart or Lispro)-rHuPH20

Arm Description

In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days.

In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days.

Outcomes

Primary Outcome Measures

Early Insulin Exposure (%AUC[0-60])

Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0 360}]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose during a euglycemic clamp.

Secondary Outcome Measures

Maximum Glucose Infusion Rate (GIRmax)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)

Early and late tGIR50%max are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time to 50% Total Glucose Infused (50%Gtot)

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Area Under the Glucose Concentration Curve (AUC[0-360])

Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Duration of Insulin Action (AUMC[0-360]/AUC[0-360])

Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]). AUCM is the total area under the first moment curve. First moment curve is obtained by plotting concentration-time versus time. It can be used to measure how long a drug stays in the body. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Full Information

NCT ID

NCT01526733

First Posted

January 31, 2012

Last Updated

February 5, 2019

Sponsor

Halozyme Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT01526733

Brief Title

Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase

Official Title

A Phase 4, Randomized, Double-Blind, 2-Way Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) With, Compared to Without, Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

December 2011 (undefined)

Primary Completion Date

August 2012 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Halozyme Therapeutics

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.

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, Continuous Subcutaneous Insulin Infusion (CSII)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Insulin (Aspart or Lispro)-Sham

Arm Type

Sham Comparator

Arm Description

In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days.

Arm Title

Insulin (Aspart or Lispro)-rHuPH20

Arm Type

Experimental

Arm Description

In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days.

Intervention Type

Drug

Intervention Name(s)

Sham Injection

Intervention Type

Drug

Intervention Name(s)

Recombinant human hyaluronidase PH20

Other Intervention Name(s)

rHuPH20, PH20, Hylenex

Intervention Type

Drug

Intervention Name(s)

Insulin aspart

Other Intervention Name(s)

Novolog, Aspart

Intervention Type

Drug

Intervention Name(s)

Insulin lispro

Other Intervention Name(s)

Humalog, Lispro

Primary Outcome Measure Information:

Title

Early Insulin Exposure (%AUC[0-60])

Description

Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0 360}]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose during a euglycemic clamp.

Time Frame

10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4

Secondary Outcome Measure Information:

Title

Maximum Glucose Infusion Rate (GIRmax)

Description

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Title

Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)

Description

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Title

Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)

Description

Early and late tGIR50%max are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Title

Time to 50% Total Glucose Infused (50%Gtot)

Description

Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Title

Area Under the Glucose Concentration Curve (AUC[0-360])

Description

Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

Title

Duration of Insulin Action (AUMC[0-360]/AUC[0-360])

Description

Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]). AUCM is the total area under the first moment curve. First moment curve is obtained by plotting concentration-time versus time. It can be used to measure how long a drug stays in the body. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

Time Frame

10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Males or females of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study. Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive. Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results. Fasting connecting peptide of insulin (C-peptide) <0.6 nanograms per milliliter (ng/mL). Current treatment with insulin <90 units per day (U/d). Current use of rapid acting insulin analog. Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening 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 the study protocol. Exclusion Criteria: Known or suspected allergy to any component of any of the study drugs in this study. Previous enrollment in this study. Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (for example, coumadin or heparin) will be excluded. Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II). Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator. Current addiction to alcohol or substances of abuse as determined by the Investigator. Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of the Screening Visit(s) in this study. Pregnancy, breastfeeding, 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, or barrier methods). Symptomatic gastroparesis. Receipt of any investigational drug within 4 weeks of Study Day 1.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Linda Morrow, MD

Organizational Affiliation

Profil Institute for Clinical Research, Inc.

Official's Role

Principal Investigator

Facility Information:

Facility Name

Profil Institute for Clinical Research

City

Chula Vista

State/Province

California

ZIP/Postal Code

91911

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.halozyme.com

Description

Sponsor's Website

Type 1 Diabetes Mellitus

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial